chr17-10411058-G-A

Variant names:

• chr17-10411058-G-A
• rs12601552
• NM_002472.3:c.1417-111C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002472.3(MYH8):​c.1417-111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,553,184 control chromosomes in the GnomAD database, including 128,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (12118 hom., cov: 32)
  • Exomes 𝑓: 0.39 (116370 hom.)
• Consequence: MYH8 NM_002472.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.26
• Publications: 4 publications found

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]

MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 17-10411058-G-A is Benign according to our data. Variant chr17-10411058-G-A is described in ClinVar as [Benign]. Clinvar id is 1181307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH8	NM_002472.3	c.1417-111C>T		intron_variant	Intron 14 of 39	ENST00000403437.2	NP_002463.2
MYHAS	NR_125367.1	n.167+4820G>A		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH8	ENST00000403437.2	c.1417-111C>T		intron_variant	Intron 14 of 39	5	NM_002472.3	ENSP00000384330.2

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57577 AN: 151830 Hom.: 12109 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.367

GnomAD4 exome AF: 0.392 AC: 549394 AN: 1401236 Hom.: 116370 AF XY: 0.398 AC XY: 277141 AN XY: 696248

African (AFR) AF: 0.269 AC: 8444 AN: 31406

American (AMR) AF: 0.563 AC: 22855 AN: 40586

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 10268 AN: 25472

East Asian (EAS) AF: 0.847 AC: 31638 AN: 37350

South Asian (SAS) AF: 0.612 AC: 50414 AN: 82380

European-Finnish (FIN) AF: 0.424 AC: 20585 AN: 48592

Middle Eastern (MID) AF: 0.414 AC: 2172 AN: 5250

European-Non Finnish (NFE) AF: 0.354 AC: 379302 AN: 1072070

Other (OTH) AF: 0.408 AC: 23716 AN: 58130

GnomAD4 genome AF: 0.379 AC: 57623 AN: 151948 Hom.: 12118 Cov.: 32 AF XY: 0.393 AC XY: 29184 AN XY: 74246

African (AFR) AF: 0.276 AC: 11441 AN: 41454

American (AMR) AF: 0.460 AC: 7015 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1377 AN: 3466

East Asian (EAS) AF: 0.866 AC: 4476 AN: 5168

South Asian (SAS) AF: 0.634 AC: 3052 AN: 4816

European-Finnish (FIN) AF: 0.436 AC: 4599 AN: 10544

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.359 AC: 24389 AN: 67936

Other (OTH) AF: 0.369 AC: 779 AN: 2110

Alfa AF: 0.354 Hom.: 1248

Bravo AF: 0.373

Asia WGS AF: 0.712 AC: 2472 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.21
DANN	Benign	0.48
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12601552; hg19: chr17-10314375; COSMIC: COSV107504935;