rs3744553

Variant names:

• chr17-10401183-C-T
• rs3744553
• NM_002472.3:c.3117G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-10401183-C-T
• chr17-10401183-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002472.3(MYH8):​c.3117G>A​(p.Gly1039Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0586 in 1,613,636 control chromosomes in the GnomAD database, including 3,202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.048 (225 hom., cov: 32)
  • Exomes 𝑓: 0.060 (2977 hom.)
• Consequence: MYH8 NM_002472.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.92
• Publications: 8 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 17-10401183-C-T is Benign according to our data. Variant chr17-10401183-C-T is described in ClinVar as Benign. ClinVar VariationId is 129673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.92 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002472.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH8	NM_002472.3	MANE Select	c.3117G>A	p.Gly1039Gly	synonymous	Exon 25 of 40	NP_002463.2	P13535
	MYHAS	NR_125367.1		n.77-4965C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH8	ENST00000403437.2	TSL:5 MANE Select	c.3117G>A	p.Gly1039Gly	synonymous	Exon 25 of 40	ENSP00000384330.2	P13535
	MYHAS	ENST00000399342.6	TSL:3	n.77-4965C>T		intron	N/A
	MYHAS	ENST00000581304.2	TSL:3	n.53-4965C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0481 AC: 7321 AN: 152076 Hom.: 224 Cov.: 32

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.0747

Gnomad AMR AF: 0.0421

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.0271

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0571

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0586

Gnomad OTH AF: 0.0637

GnomAD2 exomes AF: 0.0578 AC: 14516 AN: 251290 AF XY: 0.0622

Gnomad AFR exome AF: 0.0183

Gnomad AMR exome AF: 0.0348

Gnomad ASJ exome AF: 0.0839

Gnomad EAS exome AF: 0.0220

Gnomad FIN exome AF: 0.0595

Gnomad NFE exome AF: 0.0586

Gnomad OTH exome AF: 0.0583

GnomAD4 exome AF: 0.0597 AC: 87180 AN: 1461442 Hom.: 2977 Cov.: 35 AF XY: 0.0613 AC XY: 44587 AN XY: 726996

African (AFR) AF: 0.0190 AC: 637 AN: 33450

American (AMR) AF: 0.0359 AC: 1606 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0857 AC: 2240 AN: 26128

East Asian (EAS) AF: 0.0285 AC: 1133 AN: 39698

South Asian (SAS) AF: 0.112 AC: 9667 AN: 86044

European-Finnish (FIN) AF: 0.0600 AC: 3205 AN: 53416

Middle Eastern (MID) AF: 0.0562 AC: 324 AN: 5766

European-Non Finnish (NFE) AF: 0.0582 AC: 64691 AN: 1111854

Other (OTH) AF: 0.0609 AC: 3677 AN: 60384

GnomAD4 genome AF: 0.0481 AC: 7324 AN: 152194 Hom.: 225 Cov.: 32 AF XY: 0.0495 AC XY: 3684 AN XY: 74388

African (AFR) AF: 0.0203 AC: 844 AN: 41534

American (AMR) AF: 0.0420 AC: 642 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0832 AC: 289 AN: 3472

East Asian (EAS) AF: 0.0272 AC: 141 AN: 5182

South Asian (SAS) AF: 0.124 AC: 596 AN: 4820

European-Finnish (FIN) AF: 0.0571 AC: 604 AN: 10578

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0586 AC: 3987 AN: 68010

Other (OTH) AF: 0.0626 AC: 132 AN: 2110

Alfa AF: 0.0488 Hom.: 185

Bravo AF: 0.0445

Asia WGS AF: 0.0700 AC: 241 AN: 3478

EpiCase AF: 0.0595

EpiControl AF: 0.0612

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Hecht syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	3.3
DANN	Benign	0.74
PhyloP100		-3.9
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: rs3744553; hg19: chr17-10304500; COSMIC: COSV67965787;