NM_002474.3:c.4239C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1

The NM_002474.3(MYH11):c.4239C>T(p.Ala1413Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000428 in 1,614,148 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

MYH11
NM_002474.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -1.23

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 16-15724287-G-A is Benign according to our data. Variant chr16-15724287-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 263393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-15724287-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.23 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00226 (344/152264) while in subpopulation AFR AF= 0.0078 (324/41538). AF 95% confidence interval is 0.0071. There are 0 homozygotes in gnomad4. There are 164 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH11	NM_002474.3 link	c.4239C>T	p.Ala1413Ala	synonymous_variant	Exon 31 of 41	ENST00000300036.6	NP_002465.1	P35749-1A0A024QZJ4
MYH11	NM_001040113.2 link	c.4260C>T	p.Ala1420Ala	synonymous_variant	Exon 32 of 43	ENST00000452625.7	NP_001035202.1	P35749-3
NDE1	NM_017668.3 link	c.*36G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000396354.6	NP_060138.1	Q9NXR1-2X5DR54

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYH11	ENST00000300036.6 link	c.4239C>T	p.Ala1413Ala	synonymous_variant	Exon 31 of 41	1	NM_002474.3	ENSP00000300036.5	P35749-1
MYH11	ENST00000452625.7 link	c.4260C>T	p.Ala1420Ala	synonymous_variant	Exon 32 of 43	1	NM_001040113.2	ENSP00000407821.2	P35749-3
NDE1	ENST00000396354.6 link	c.*36G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_017668.3	ENSP00000379642.1	Q9NXR1-2

Frequencies

GnomAD3 genomes

AF:

0.00225

AC:

343

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00780

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00

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:

0.00143

GnomAD3 exomes

AF:

0.000592

AC:

149

AN:

251478

Hom.:

AF XY:

0.000441

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00781

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000237

AC:

347

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

147

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00809

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.00226

AC:

344

AN:

152264

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

164

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00780

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000998

Hom.:

Bravo

AF:

0.00267

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 28, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 14, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:4

Feb 05, 2024

All of Us Research Program, National Institutes of Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 27, 2016

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Nov 08, 2017

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 25, 2018

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jul 30, 2021

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aortic aneurysm, familial thoracic 4

Benign:1

Dec 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

5.1

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over