rs8068729

Variant names:

• chr17-10415319-A-G
• rs8068729
• NM_002472.3:c.714T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-10415319-A-G
• chr17-10415319-A-T

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.714T>C​(p.Thr238Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.929 in 1,613,968 control chromosomes in the GnomAD database, including 699,091 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (58523 hom., cov: 32)
  • Exomes 𝑓: 0.93 (640568 hom.)
• Consequence: MYH8 NM_002472.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -5.56
• Publications: 17 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=-0.94).
• BP6: Variant 17-10415319-A-G is Benign according to our data. Variant chr17-10415319-A-G is described in ClinVar as Benign. ClinVar VariationId is 129680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.56 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.714T>C	p.Thr238Thr	synonymous	Exon 8 of 40	NP_002463.2	P13535
	MYHAS	NR_125367.1		n.167+9081A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH8	ENST00000403437.2	TSL:5 MANE Select	c.714T>C	p.Thr238Thr	synonymous	Exon 8 of 40	ENSP00000384330.2	P13535
	MYHAS	ENST00000399342.6	TSL:3	n.206+9042A>G		intron	N/A
	MYHAS	ENST00000581304.2	TSL:3	n.143+9081A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.869 AC: 132064 AN: 152058 Hom.: 58491 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.943

Gnomad OTH AF: 0.854

GnomAD2 exomes AF: 0.929 AC: 233517 AN: 251440 AF XY: 0.932

Gnomad AFR exome AF: 0.663

Gnomad AMR exome AF: 0.950

Gnomad ASJ exome AF: 0.923

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.976

Gnomad NFE exome AF: 0.942

Gnomad OTH exome AF: 0.927

GnomAD4 exome AF: 0.935 AC: 1366715 AN: 1461792 Hom.: 640568 Cov.: 68 AF XY: 0.935 AC XY: 680307 AN XY: 727214

African (AFR) AF: 0.662 AC: 22155 AN: 33474

American (AMR) AF: 0.947 AC: 42363 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.927 AC: 24218 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39689 AN: 39700

South Asian (SAS) AF: 0.921 AC: 79479 AN: 86252

European-Finnish (FIN) AF: 0.973 AC: 51997 AN: 53420

Middle Eastern (MID) AF: 0.826 AC: 4755 AN: 5760

European-Non Finnish (NFE) AF: 0.941 AC: 1046529 AN: 1111930

Other (OTH) AF: 0.919 AC: 55530 AN: 60396

GnomAD4 genome AF: 0.868 AC: 132153 AN: 152176 Hom.: 58523 Cov.: 32 AF XY: 0.873 AC XY: 64943 AN XY: 74416

African (AFR) AF: 0.676 AC: 28018 AN: 41460

American (AMR) AF: 0.908 AC: 13906 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.925 AC: 3213 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5165 AN: 5172

South Asian (SAS) AF: 0.922 AC: 4441 AN: 4818

European-Finnish (FIN) AF: 0.980 AC: 10405 AN: 10612

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.943 AC: 64171 AN: 68018

Other (OTH) AF: 0.856 AC: 1807 AN: 2110

Alfa AF: 0.907 Hom.: 52771

Bravo AF: 0.854

Asia WGS AF: 0.950 AC: 3305 AN: 3478

EpiCase AF: 0.935

EpiControl AF: 0.934

ClinVar

ClinVar submissions

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	-0.94
CADD	Benign	0.22
DANN	Benign	0.51
PhyloP100		-5.6
Mutation Taster		=98/2	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: rs8068729; hg19: chr17-10318636; COSMIC: COSV108242432;