rs33969260

Variant names:

• chr17-10393169-G-A
• rs33969260
• NM_002472.3:c.5208C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-10393169-G-A
• chr17-10393169-G-C

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.5208C>T​(p.Asp1736Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,613,884 control chromosomes in the GnomAD database, including 41,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2878 hom., cov: 32)
  • Exomes 𝑓: 0.22 (39118 hom.)
• Consequence: MYH8 NM_002472.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.0750
• Publications: 11 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=-0.51).
• BP6: Variant 17-10393169-G-A is Benign according to our data. Variant chr17-10393169-G-A is described in ClinVar as Benign. ClinVar VariationId is 129679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.075 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 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.5208C>T	p.Asp1736Asp	synonymous	Exon 36 of 40	NP_002463.2
	MYHAS	NR_125367.1		n.76+9962G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH8	ENST00000403437.2	TSL:5 MANE Select	c.5208C>T	p.Asp1736Asp	synonymous	Exon 36 of 40	ENSP00000384330.2
	MYHAS	ENST00000399342.6	TSL:3	n.76+9962G>A		intron	N/A
	MYHAS	ENST00000581304.2	TSL:3	n.52+9962G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25559 AN: 152002 Hom.: 2879 Cov.: 32

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.197

GnomAD2 exomes AF: 0.175 AC: 43906 AN: 251370 AF XY: 0.178

Gnomad AFR exome AF: 0.0445

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.262

Gnomad EAS exome AF: 0.000544

Gnomad FIN exome AF: 0.203

Gnomad NFE exome AF: 0.251

Gnomad OTH exome AF: 0.217

GnomAD4 exome AF: 0.221 AC: 322319 AN: 1461764 Hom.: 39118 Cov.: 37 AF XY: 0.217 AC XY: 158148 AN XY: 727180

African (AFR) AF: 0.0434 AC: 1454 AN: 33480

American (AMR) AF: 0.123 AC: 5482 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 6833 AN: 26130

East Asian (EAS) AF: 0.000378 AC: 15 AN: 39700

South Asian (SAS) AF: 0.0800 AC: 6900 AN: 86256

European-Finnish (FIN) AF: 0.209 AC: 11173 AN: 53416

Middle Eastern (MID) AF: 0.218 AC: 1258 AN: 5768

European-Non Finnish (NFE) AF: 0.249 AC: 276878 AN: 1111906

Other (OTH) AF: 0.204 AC: 12326 AN: 60384

GnomAD4 genome AF: 0.168 AC: 25557 AN: 152120 Hom.: 2878 Cov.: 32 AF XY: 0.164 AC XY: 12158 AN XY: 74360

African (AFR) AF: 0.0508 AC: 2108 AN: 41514

American (AMR) AF: 0.157 AC: 2404 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 904 AN: 3470

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5192

South Asian (SAS) AF: 0.0710 AC: 342 AN: 4816

European-Finnish (FIN) AF: 0.204 AC: 2151 AN: 10552

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16901 AN: 67982

Other (OTH) AF: 0.196 AC: 413 AN: 2112

Alfa AF: 0.222 Hom.: 2106

Bravo AF: 0.163

Asia WGS AF: 0.0420 AC: 147 AN: 3478

EpiCase AF: 0.259

EpiControl AF: 0.256

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Hecht syndrome (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	4.7
DANN	Benign	0.74
PhyloP100		-0.075
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs33969260; hg19: chr17-10296486; COSMIC: COSV67960032;