chr16-15718451-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_002474.3(MYH11):c.5172-13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,549,502 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

MYH11
NM_002474.3 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:5

Conservation

PhyloP100: 0.683

Publications

1 publications found

Variant links:

Genes affected

MYH11 (HGNC:7569): (myosin heavy chain 11) The protein encoded by this gene is a smooth muscle myosin belonging to the myosin heavy chain family. The gene product is a subunit of a hexameric protein that consists of two heavy chain subunits and two pairs of non-identical light chain subunits. It functions as a major contractile protein, converting chemical energy into mechanical energy through the hydrolysis of ATP. A chromosomal rearrangement involving this gene is associated with acute myeloid leukemia of the M4Eo subtype. Mutations in this gene are associated with visceral myopathy, megacystis-microcolon-intestinal hypoperistalsis syndrome 2, and familial thoracic aortic aneurysm 4. [provided by RefSeq, May 2022]

MYH11 links:

NDE1 (HGNC:17619): (nudE neurodevelopment protein 1) This gene encodes a member of the nuclear distribution E (NudE) family of proteins. The encoded protein is localized at the centrosome and interacts with other centrosome components as part of a multiprotein complex that regulates dynein function. This protein plays an essential role in microtubule organization, mitosis and neuronal migration. Mutations in this gene cause lissencephaly 4, a disorder characterized by lissencephaly, severe brain atrophy, microcephaly, and severe cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

NDE1 Gene-Disease associations (from GenCC):

lissencephaly 4
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
hydranencephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
microlissencephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
NDE1-related microhydranencephaly
Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

NDE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-15718451-C-T is Benign according to our data. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036. Variant chr16-15718451-C-T is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 201036.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000177 (27/152286) while in subpopulation AFR AF = 0.00012 (5/41576). AF 95% confidence interval is 0.0000473. There are 0 homozygotes in GnomAd4. There are 12 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYH11	NM_002474.3 link	c.5172-13G>A	intron_variant	Intron 36 of 40	ENST00000300036.6	NP_002465.1	P35749-1A0A024QZJ4
MYH11	NM_001040113.2 link	c.5193-13G>A	intron_variant	Intron 37 of 42	ENST00000452625.7	NP_001035202.1	P35749-3
NDE1	NM_017668.3 link	c.948-5740C>T	intron_variant	Intron 8 of 8	ENST00000396354.6	NP_060138.1	Q9NXR1-2X5DR54

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYH11	ENST00000300036.6 link	c.5172-13G>A	intron_variant	Intron 36 of 40	1	NM_002474.3	ENSP00000300036.5	P35749-1
MYH11	ENST00000452625.7 link	c.5193-13G>A	intron_variant	Intron 37 of 42	1	NM_001040113.2	ENSP00000407821.2	P35749-3
NDE1	ENST00000396354.6 link	c.948-5740C>T	intron_variant	Intron 8 of 8	1	NM_017668.3	ENSP00000379642.1	Q9NXR1-2

Frequencies

GnomAD3 genomes

AF:

0.000177

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000332

AC:

AN:

159540

AF XY:

0.000349

show subpopulations

Gnomad AFR exome

AF:

0.000106

Gnomad AMR exome

AF:

0.0000388

Gnomad ASJ exome

AF:

0.00491

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000458

Gnomad OTH exome

AF:

0.00108

GnomAD4 exome

AF:

0.000129

AC:

180

AN:

1397216

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

691144

show subpopulations

African (AFR)

AF:

0.0000312

AC:

AN:

32096

American (AMR)

AF:

0.0000270

AC:

AN:

37060

Ashkenazi Jewish (ASJ)

AF:

0.00552

AC:

140

AN:

25362

East Asian (EAS)

AF:

0.0000273

AC:

AN:

36590

South Asian (SAS)

AF:

0.0000122

AC:

AN:

81678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38710

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4754

European-Non Finnish (NFE)

AF:

0.0000249

AC:

AN:

1082864

Other (OTH)

AF:

0.000155

AC:

AN:

58102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000177

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41576

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00519

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68016

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000781

Hom.:

Bravo

AF:

0.000151

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Aortic aneurysm, familial thoracic 4

Uncertain:1Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Jan 19, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Nov 11, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Jul 14, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.5193-13G>A in intron 37 of MYH11: This variant is not expected to have clinica l significance because it is not located within the splice consensus sequence. I t has been identified in 0.1% (11/11814) of European chromosomes by the Exome Ag gregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs373378619). -

Familial thoracic aortic aneurysm and aortic dissection

Benign:2

Feb 05, 2024

All of Us Research Program, National Institutes of Health

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 16, 2018

Color Diagnostics, LLC DBA Color Health

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Lissencephaly, Recessive

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.3

(source)

DANN

Benign

0.76

PhyloP100

0.68

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over