17-10494438-G-A

Variant names:

• chr17-10494438-G-A
• rs151180649
• NM_005963.4:c.5583C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_005963.4(MYH1):​c.5583C>T​(p.Asp1861Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00451 in 1,613,526 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (30 hom.)
• Consequence: MYH1 NM_005963.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.30
• Publications: 3 publications found

Genes affected

MYH1 (HGNC:7567): (myosin heavy chain 1) Myosin is a major contractile protein which converts chemical energy into mechanical energy through the hydrolysis of ATP. Myosin is a hexameric protein composed of a pair of myosin heavy chains (MYH) and two pairs of nonidentical light chains. Myosin heavy chains are encoded by a multigene family. In mammals at least 10 different myosin heavy chain (MYH) isoforms have been described from striated, smooth, and nonmuscle cells. These isoforms show expression that is spatially and temporally regulated during development. [provided by RefSeq, Jul 2008]

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 17-10494438-G-A is Benign according to our data. Variant chr17-10494438-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2647475.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.3 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH1	NM_005963.4	c.5583C>T	p.Asp1861Asp	synonymous_variant	Exon 39 of 40	ENST00000226207.6	NP_005954.3
MYH1	XM_017024675.2	c.5583C>T	p.Asp1861Asp	synonymous_variant	Exon 39 of 40		XP_016880164.1
MYHAS	NR_125367.1	n.168-73099G>A		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH1	ENST00000226207.6	c.5583C>T	p.Asp1861Asp	synonymous_variant	Exon 39 of 40	5	NM_005963.4	ENSP00000226207.5

Frequencies

GnomAD3 genomes AF: 0.00273 AC: 416 AN: 152118 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00432

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00274 AC: 688 AN: 250810 AF XY: 0.00288

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00232

Gnomad ASJ exome AF: 0.000598

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000508

Gnomad NFE exome AF: 0.00406

Gnomad OTH exome AF: 0.00441

GnomAD4 exome AF: 0.00470 AC: 6869 AN: 1461290 Hom.: 30 Cov.: 32 AF XY: 0.00464 AC XY: 3370 AN XY: 726930

African (AFR) AF: 0.000658 AC: 22 AN: 33434

American (AMR) AF: 0.00240 AC: 107 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.000651 AC: 17 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00304 AC: 262 AN: 86078

European-Finnish (FIN) AF: 0.000618 AC: 33 AN: 53414

Middle Eastern (MID) AF: 0.00503 AC: 29 AN: 5766

European-Non Finnish (NFE) AF: 0.00550 AC: 6114 AN: 1111854

Other (OTH) AF: 0.00472 AC: 285 AN: 60364

GnomAD4 genome AF: 0.00273 AC: 416 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.00253 AC XY: 188 AN XY: 74418

African (AFR) AF: 0.00101 AC: 42 AN: 41534

American (AMR) AF: 0.00177 AC: 27 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00208 AC: 10 AN: 4816

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10608

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00432 AC: 294 AN: 68024

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00358 Hom.: 1

Bravo AF: 0.00294

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00436

EpiControl AF: 0.00427

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MYH1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	7.2
DANN	Benign	0.73
PhyloP100		2.3
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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: rs151180649; hg19: chr17-10397755;