Variant 17-10445037-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_017533.2(MYH4):c.5405A>G(p.Asp1802Gly) variant causes a missense change. The variant allele was found at a frequency of 0.379 in 1,613,872 control chromosomes in the GnomAD database, including 124,462 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.36 ( 11081 hom., cov: 32)

Exomes 𝑓: 0.38 ( 113381 hom. )

Consequence

MYH4
NM_017533.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.23

Variant links:

Genes affected

MYH4 (HGNC:7574): (myosin heavy chain 4) Enables double-stranded RNA binding activity. Involved in muscle contraction. Located in myofibril. [provided by Alliance of Genome Resources, Apr 2022]

MYH4 links:

ENSG00000272736 (HGNC:):

ENSG00000272736 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 17-10445037-T-C is Benign according to our data. Variant chr17-10445037-T-C is described in ClinVar as [Benign]. Clinvar id is 1225242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH4	NM_017533.2 linkuse as main transcript	c.5405A>G	p.Asp1802Gly	missense_variant	37/40	ENST00000255381.2	NP_060003.2
MYH4	XM_017024676.2 linkuse as main transcript	c.5405A>G	p.Asp1802Gly	missense_variant	35/38		XP_016880165.1	Q9Y623
MYHAS	NR_125367.1 linkuse as main transcript	n.167+38799T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYH4	ENST00000255381.2 linkuse as main transcript	c.5405A>G	p.Asp1802Gly	missense_variant	37/40	1	NM_017533.2	ENSP00000255381.2	Q9Y623
ENSG00000272736	ENST00000399342.6 linkuse as main transcript	n.206+38760T>C		intron_variant		3
ENSG00000272736	ENST00000581304.1 linkuse as main transcript	n.143+38799T>C		intron_variant		3
MYHAS	ENST00000587182.2 linkuse as main transcript	n.155+38799T>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55331

AN:

151906

Hom.:

11082

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.421

Gnomad AMR

AF:

0.444

Gnomad ASJ

AF:

0.364

Gnomad EAS

AF:

0.816

Gnomad SAS

AF:

0.514

Gnomad FIN

AF:

0.427

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.324

GnomAD3 exomes

AF:

0.437

AC:

109971

AN:

251462

Hom.:

26905

AF XY:

0.434

AC XY:

59015

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.563

Gnomad ASJ exome

AF:

0.361

Gnomad EAS exome

AF:

0.839

Gnomad SAS exome

AF:

0.509

Gnomad FIN exome

AF:

0.422

Gnomad NFE exome

AF:

0.353

Gnomad OTH exome

AF:

0.395

GnomAD4 exome

AF:

0.381

AC:

556496

AN:

1461848

Hom.:

113381

Cov.:

103

AF XY:

0.384

AC XY:

278908

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.545

Gnomad4 ASJ exome

AF:

0.361

Gnomad4 EAS exome

AF:

0.808

Gnomad4 SAS exome

AF:

0.508

Gnomad4 FIN exome

AF:

0.413

Gnomad4 NFE exome

AF:

0.351

Gnomad4 OTH exome

AF:

0.387

GnomAD4 genome

AF:

0.364

AC:

55353

AN:

152024

Hom.:

11081

Cov.:

AF XY:

0.376

AC XY:

27947

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.259

Gnomad4 AMR

AF:

0.445

Gnomad4 ASJ

AF:

0.364

Gnomad4 EAS

AF:

0.815

Gnomad4 SAS

AF:

0.513

Gnomad4 FIN

AF:

0.427

Gnomad4 NFE

AF:

0.356

Gnomad4 OTH

AF:

0.324

Alfa

AF:

0.357

Hom.:

3628

Bravo

AF:

0.359

TwinsUK

AF:

0.348

AC:

1292

ALSPAC

AF:

0.354

AC:

1366

ESP6500AA

AF:

0.258

AC:

1137

ESP6500EA

AF:

0.355

AC:

3050

ExAC

AF:

0.428

AC:

51975

Asia WGS

AF:

0.595

AC:

2068

AN:

3478

EpiCase

AF:

0.342

EpiControl

AF:

0.345

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 09, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

Eigen

Pathogenic

0.76

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0000033

MetaSVM

Benign

-0.91

MutationAssessor

Pathogenic

3.5

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-4.5

REVEL

Uncertain

0.52

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.042

Polyphen

0.99

Vest4

0.15

MPC

0.22

ClinPred

0.054

GERP RS

5.5

Varity_R

0.23

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.57

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.57

Position offset: 1

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