Variant rs150008607 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4BS2

The NM_002472.3(MYH8):c.3874C>T(p.Arg1292Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,612,060 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

MYH8
NM_002472.3 stop_gained

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.611

Variant links:

Genes affected

MYH8 (HGNC:7578): (myosin heavy chain 8) Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is predominantly expressed in fetal skeletal muscle. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in trismus-pseudocamptodactyly syndrome. [provided by RefSeq, Sep 2009]

MYH8 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM4

Stoplost variant in NM_002472.3 Downstream stopcodon found after 49 codons.

BS2

High AC in GnomAd at 46 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH8	NM_002472.3 linkuse as main transcript	c.3874C>T	p.Arg1292Ter	stop_gained	29/40	ENST00000403437.2
MYHAS	NR_125367.1 linkuse as main transcript	n.77-7273G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MYH8	ENST00000403437.2 linkuse as main transcript	c.3874C>T	p.Arg1292Ter	stop_gained	29/40	5	NM_002472.3	P1
	ENST00000399342.6 linkuse as main transcript	n.77-7273G>A		intron_variant, non_coding_transcript_variant		3
	ENST00000581304.1 linkuse as main transcript	n.53-7273G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000303

AC:

AN:

151736

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00715

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000482

GnomAD3 exomes

AF:

0.000707

AC:

177

AN:

250406

Hom.:

AF XY:

0.000598

AC XY:

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00892

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000164

AC:

239

AN:

1460210

Hom.:

Cov.:

AF XY:

0.000131

AC XY:

AN XY:

726534

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00471

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.0000192

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.000303

AC:

AN:

151850

Hom.:

Cov.:

AF XY:

0.000337

AC XY:

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00717

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000477

Alfa

AF:

0.000394

Hom.:

Bravo

AF:

0.000419

ExAC

AF:

0.000593

AC:

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hecht syndrome;C1837245:Carney complex - trismus - pseudocamptodactyly syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

reference population

Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center

Mar 18, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.62

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Uncertain

0.41

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.60

MutationTaster

Benign

1.0

Vest4

0.86

GERP RS

4.3

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

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