Variant 17-10400593-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate

The NM_002472.3(MYH8):c.3532C>A(p.Arg1178Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

MYH8
NM_002472.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.31

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:

ENSG00000272736 (HGNC:):

ENSG00000272736 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MYH8. . Gene score misZ 0.34953 (greater than the threshold 3.09). Trascript score misZ 3.2125 (greater than threshold 3.09). GenCC has associacion of gene with trismus-pseudocamptodactyly syndrome, Carney complex - trismus - pseudocamptodactyly syndrome.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.883

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH8	NM_002472.3 linkuse as main transcript	c.3532C>A	p.Arg1178Ser	missense_variant	27/40	ENST00000403437.2	NP_002463.2	P13535
MYHAS	NR_125367.1 linkuse as main transcript	n.77-5555G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MYH8	ENST00000403437.2 linkuse as main transcript	c.3532C>A	p.Arg1178Ser	missense_variant	27/40	5	NM_002472.3	ENSP00000384330.2	P13535
ENSG00000272736	ENST00000399342.6 linkuse as main transcript	n.77-5555G>T		intron_variant		3
ENSG00000272736	ENST00000581304.1 linkuse as main transcript	n.53-5555G>T		intron_variant		3
MYHAS	ENST00000587182.2 linkuse as main transcript	n.65-5555G>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.040

MetaRNN

Pathogenic

0.88

MetaSVM

Uncertain

0.69

MutationAssessor

Pathogenic

4.3

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-4.1

REVEL

Pathogenic

0.77

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.69

MutPred

0.74

Gain of phosphorylation at R1178 (P = 0.0243);

MVP

0.86

MPC

0.83

ClinPred

1.0

GERP RS

4.4

Varity_R

0.64

gMVP

0.84

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over