chr17-10393705-C-A

Position:

• chr17-10393705-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002472.3(MYH8):​c.5167-495G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,000 control chromosomes in the GnomAD database, including 23,559 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (23559 hom., cov: 32)
• Consequence: MYH8 NM_002472.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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]

ENSG00000272736 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH8	NM_002472.3	c.5167-495G>T		intron_variant		ENST00000403437.2	NP_002463.2
MYHAS	NR_125367.1	n.76+10498C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH8	ENST00000403437.2	c.5167-495G>T		intron_variant		5	NM_002472.3	ENSP00000384330.2
ENSG00000272736	ENST00000399342.6	n.76+10498C>A		intron_variant		3
ENSG00000272736	ENST00000581304.1	n.52+10498C>A		intron_variant		3
MYHAS	ENST00000587182.2	n.64+10498C>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83333 AN: 151882 Hom.: 23550 Cov.: 32

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.587

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.549 AC: 83378 AN: 152000 Hom.: 23559 Cov.: 32 AF XY: 0.537 AC XY: 39859 AN XY: 74290

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.497

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.586

Alfa AF: 0.579 Hom.: 4193

Bravo AF: 0.553

Asia WGS AF: 0.269 AC: 941 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.022
DANN	Benign	0.37

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

Other links and lift over

dbSNP: rs7211175; hg19: chr17-10297022; COSMIC: COSV67971322;