Variant 16-15703925-G-GT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_002474.3(MYH11):c.*65_*66insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00498 in 1,606,278 control chromosomes in the GnomAD database, including 333 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.027 ( 178 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 155 hom. )

Consequence

MYH11
NM_002474.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.794

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 -10 ACMG points.

BP6

Variant 16-15703925-G-GT is Benign according to our data. Variant chr16-15703925-G-GT is described in ClinVar as [Benign]. Clinvar id is 1294395.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
MYH11	NM_001040113.2 linkuse as main transcript	c.206_207insA	3_prime_UTR_variant	43/43	ENST00000452625.7
MYH11	NM_002474.3 linkuse as main transcript	c.65_66insA	3_prime_UTR_variant	41/41	ENST00000300036.6
NDE1	NM_017668.3 linkuse as main transcript	c.947+7073dup	intron_variant		ENST00000396354.6

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH11	ENST00000300036.6 linkuse as main transcript	c.65_66insA	3_prime_UTR_variant	41/41	1	NM_002474.3	P3	P35749-1
MYH11	ENST00000452625.7 linkuse as main transcript	c.206_207insA	3_prime_UTR_variant	43/43	1	NM_001040113.2		P35749-3
NDE1	ENST00000396354.6 linkuse as main transcript	c.947+7073dup	intron_variant		1	NM_017668.3	P1	Q9NXR1-2

Frequencies

GnomAD3 genomes

AF:

0.0270

AC:

4098

AN:

151678

Hom.:

178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0948

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00933

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0168

GnomAD3 exomes

AF:

0.00697

AC:

1742

AN:

249778

Hom.:

AF XY:

0.00520

AC XY:

703

AN XY:

135118

show subpopulations

Gnomad AFR exome

AF:

0.0952

Gnomad AMR exome

AF:

0.00489

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00197

GnomAD4 exome

AF:

0.00267

AC:

3889

AN:

1454482

Hom.:

155

Cov.:

AF XY:

0.00226

AC XY:

1634

AN XY:

723972

show subpopulations

Gnomad4 AFR exome

AF:

0.0929

Gnomad4 AMR exome

AF:

0.00537

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000303

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000136

Gnomad4 OTH exome

AF:

0.00598

GnomAD4 genome

AF:

0.0271

AC:

4110

AN:

151796

Hom.:

178

Cov.:

AF XY:

0.0257

AC XY:

1905

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.0949

Gnomad4 AMR

AF:

0.00926

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.0166

Bravo

AF:

0.0311

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 11, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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