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. Variant got -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

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]

ENSG00000272736 (HGNC:):

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

Verdict is Benign. Variant got -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 id is 129680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-10415319-A-G is described in Lovd as [Benign].
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH8	NM_002472.3	c.714T>C	p.Thr238Thr	synonymous_variant	Exon 8 of 40	ENST00000403437.2	NP_002463.2
MYHAS	NR_125367.1	n.167+9081A>G		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH8	ENST00000403437.2	c.714T>C	p.Thr238Thr	synonymous_variant	Exon 8 of 40	5	NM_002472.3	ENSP00000384330.2
ENSG00000272736	ENST00000399342.6	n.206+9042A>G		intron_variant	Intron 2 of 3	3
ENSG00000272736	ENST00000581304.1	n.143+9081A>G		intron_variant	Intron 2 of 3	3
MYHAS	ENST00000587182.2	n.155+9081A>G		intron_variant	Intron 2 of 10	5

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

GnomAD3 exomes AF: 0.929 AC: 233517 AN: 251440 Hom.: 109106 AF XY: 0.932 AC XY: 126623 AN XY: 135878

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 SAS exome AF: 0.924

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

Gnomad4 AFR exome AF: 0.662

Gnomad4 AMR exome AF: 0.947

Gnomad4 ASJ exome AF: 0.927

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.921

Gnomad4 FIN exome AF: 0.973

Gnomad4 NFE exome AF: 0.941

Gnomad4 OTH exome AF: 0.919

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

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.908

Gnomad4 ASJ AF: 0.925

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.922

Gnomad4 FIN AF: 0.980

Gnomad4 NFE AF: 0.943

Gnomad4 OTH AF: 0.856

Alfa AF: 0.909 Hom.: 39052

Bravo AF: 0.854

Asia WGS AF: 0.950 AC: 3305 AN: 3478

EpiCase AF: 0.935

EpiControl AF: 0.934

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Hecht syndrome Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.22
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs8068729; hg19: chr17-10318636;