rs12936716

Variant names:

• chr17-10406929-G-A
• rs12936716
• NM_002472.3:c.2016C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-10406929-G-A
• chr17-10406929-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002472.3(MYH8):​c.2016C>T​(p.Phe672Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0568 in 1,613,586 control chromosomes in the GnomAD database, including 3,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (237 hom., cov: 32)
  • Exomes 𝑓: 0.057 (2775 hom.)
• Consequence: MYH8 NM_002472.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.183
• 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 17-10406929-G-A is Benign according to our data. Variant chr17-10406929-G-A is described in ClinVar as Benign. ClinVar VariationId is 129672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.183 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 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.2016C>T	p.Phe672Phe	synonymous	Exon 18 of 40	NP_002463.2	P13535
	MYHAS	NR_125367.1		n.167+691G>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.2016C>T	p.Phe672Phe	synonymous	Exon 18 of 40	ENSP00000384330.2	P13535
	MYHAS	ENST00000399342.6	TSL:3	n.206+652G>A		intron	N/A
	MYHAS	ENST00000581304.2	TSL:3	n.143+691G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0521 AC: 7919 AN: 152090 Hom.: 235 Cov.: 32

Gnomad AFR AF: 0.0406

Gnomad AMI AF: 0.0582

Gnomad AMR AF: 0.0434

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0528

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0562

Gnomad OTH AF: 0.0654

GnomAD2 exomes AF: 0.0564 AC: 14168 AN: 251414 AF XY: 0.0602

Gnomad AFR exome AF: 0.0393

Gnomad AMR exome AF: 0.0352

Gnomad ASJ exome AF: 0.0800

Gnomad EAS exome AF: 0.0229

Gnomad FIN exome AF: 0.0546

Gnomad NFE exome AF: 0.0547

Gnomad OTH exome AF: 0.0560

GnomAD4 exome AF: 0.0573 AC: 83776 AN: 1461380 Hom.: 2775 Cov.: 32 AF XY: 0.0589 AC XY: 42841 AN XY: 727022

African (AFR) AF: 0.0418 AC: 1399 AN: 33474

American (AMR) AF: 0.0363 AC: 1622 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0811 AC: 2118 AN: 26130

East Asian (EAS) AF: 0.0288 AC: 1142 AN: 39694

South Asian (SAS) AF: 0.108 AC: 9289 AN: 86228

European-Finnish (FIN) AF: 0.0538 AC: 2873 AN: 53416

Middle Eastern (MID) AF: 0.0560 AC: 323 AN: 5768

European-Non Finnish (NFE) AF: 0.0553 AC: 61428 AN: 1111564

Other (OTH) AF: 0.0593 AC: 3582 AN: 60382

GnomAD4 genome AF: 0.0521 AC: 7933 AN: 152206 Hom.: 237 Cov.: 32 AF XY: 0.0534 AC XY: 3972 AN XY: 74416

African (AFR) AF: 0.0408 AC: 1695 AN: 41542

American (AMR) AF: 0.0434 AC: 663 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3468

East Asian (EAS) AF: 0.0283 AC: 147 AN: 5186

South Asian (SAS) AF: 0.118 AC: 568 AN: 4810

European-Finnish (FIN) AF: 0.0528 AC: 559 AN: 10596

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0562 AC: 3819 AN: 67998

Other (OTH) AF: 0.0643 AC: 136 AN: 2116

Alfa AF: 0.0559 Hom.: 298

Bravo AF: 0.0492

Asia WGS AF: 0.0710 AC: 245 AN: 3478

EpiCase AF: 0.0574

EpiControl AF: 0.0575

ClinVar

ClinVar submissions as Germline

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	-0.43
CADD	Benign	0.79
DANN	Benign	0.81
PhyloP100		0.18
Mutation Taster		=70/30	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs12936716; hg19: chr17-10310246; COSMIC: COSV67965791;