Variant 17-10494438-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_005963.4(MYH1):c.5583C>T(p.Asp1861=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00451 in 1,613,526 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 30 hom. )

Consequence

MYH1
NM_005963.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.30

Variant links:

Genes affected

MYH1 (HGNC:7567): (myosin heavy chain 1) Myosin is a major contractile protein which converts chemical energy into mechanical energy through the hydrolysis of ATP. Myosin is a hexameric protein composed of a pair of myosin heavy chains (MYH) and two pairs of nonidentical light chains. Myosin heavy chains are encoded by a multigene family. In mammals at least 10 different myosin heavy chain (MYH) isoforms have been described from striated, smooth, and nonmuscle cells. These isoforms show expression that is spatially and temporally regulated during development. [provided by RefSeq, Jul 2008]

MYH1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 17-10494438-G-A is Benign according to our data. Variant chr17-10494438-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2647475.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.3 with no splicing effect.

BS2

High AC in GnomAd4 at 416 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MYH1	NM_005963.4 linkuse as main transcript	c.5583C>T	p.Asp1861=	synonymous_variant	39/40	ENST00000226207.6	NP_005954.3
MYHAS	NR_125367.1 linkuse as main transcript	n.168-73099G>A		intron_variant, non_coding_transcript_variant
MYH1	XM_017024675.2 linkuse as main transcript	c.5583C>T	p.Asp1861=	synonymous_variant	39/40		XP_016880164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MYH1	ENST00000226207.6 linkuse as main transcript	c.5583C>T	p.Asp1861=	synonymous_variant	39/40	5	NM_005963.4	ENSP00000226207	P1
	ENST00000399342.6 linkuse as main transcript	n.207-38886G>A		intron_variant, non_coding_transcript_variant		3
	ENST00000581304.1 linkuse as main transcript	n.144-38886G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00273

AC:

416

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00432

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00274

AC:

688

AN:

250810

Hom.:

AF XY:

0.00288

AC XY:

390

AN XY:

135526

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00232

Gnomad ASJ exome

AF:

0.000598

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00296

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.00406

Gnomad OTH exome

AF:

0.00441

GnomAD4 exome

AF:

0.00470

AC:

6869

AN:

1461290

Hom.:

Cov.:

AF XY:

0.00464

AC XY:

3370

AN XY:

726930

show subpopulations

Gnomad4 AFR exome

AF:

0.000658

Gnomad4 AMR exome

AF:

0.00240

Gnomad4 ASJ exome

AF:

0.000651

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00304

Gnomad4 FIN exome

AF:

0.000618

Gnomad4 NFE exome

AF:

0.00550

Gnomad4 OTH exome

AF:

0.00472

GnomAD4 genome

AF:

0.00273

AC:

416

AN:

152236

Hom.:

Cov.:

AF XY:

0.00253

AC XY:

188

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00208

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00432

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00358

Hom.:

Bravo

AF:

0.00294

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00436

EpiControl

AF:

0.00427

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

MYH1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

7.2

DANN

Benign

0.73

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