chr17-10412958-C-T

Position:

• chr17-10412958-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002472.3(MYH8):​c.1148-230G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 152,058 control chromosomes in the GnomAD database, including 12,098 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (12098 hom., cov: 32)
• Consequence: MYH8 NM_002472.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.483

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-10412958-C-T is Benign according to our data. Variant chr17-10412958-C-T is described in ClinVar as [Benign]. Clinvar id is 1277987.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH8	NM_002472.3	c.1148-230G>A		intron_variant		ENST00000403437.2	NP_002463.2
MYHAS	NR_125367.1	n.167+6720C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH8	ENST00000403437.2	c.1148-230G>A		intron_variant		5	NM_002472.3	ENSP00000384330.2
ENSG00000272736	ENST00000399342.6	n.206+6681C>T		intron_variant		3
ENSG00000272736	ENST00000581304.1	n.143+6720C>T		intron_variant		3
MYHAS	ENST00000587182.2	n.155+6720C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57515 AN: 151940 Hom.: 12089 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.379 AC: 57561 AN: 152058 Hom.: 12098 Cov.: 32 AF XY: 0.393 AC XY: 29183 AN XY: 74324

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.459

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.369

Alfa AF: 0.230 Hom.: 494

Bravo AF: 0.372

Asia WGS AF: 0.711 AC: 2461 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.67

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: rs2041125; hg19: chr17-10316275; COSMIC: COSV67961938;