rs34613390

Variant names:

• chr17-10415580-G-A
• rs34613390
• NM_002472.3:c.540C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-10415580-G-A
• chr17-10415580-G-T

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_002472.3(MYH8):​c.540C>T​(p.Thr180Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00076 in 1,614,076 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (3 hom.)
• Consequence: MYH8 NM_002472.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.00003167
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.37

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 17-10415580-G-A is Benign according to our data. Variant chr17-10415580-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 211568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-10415580-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-1.37 with no splicing effect.
• BS2: High AC in GnomAd4 at 513 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH8	NM_002472.3	c.540C>T	p.Thr180Thr	splice_region_variant, synonymous_variant	Exon 7 of 40	ENST00000403437.2	NP_002463.2
MYHAS	NR_125367.1	n.167+9342G>A		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH8	ENST00000403437.2	c.540C>T	p.Thr180Thr	splice_region_variant, synonymous_variant	Exon 7 of 40	5	NM_002472.3	ENSP00000384330.2
ENSG00000272736	ENST00000399342.6	n.206+9303G>A		intron_variant	Intron 2 of 3	3
ENSG00000272736	ENST00000581304.1	n.143+9342G>A		intron_variant	Intron 2 of 3	3
MYHAS	ENST00000587182.2	n.155+9342G>A		intron_variant	Intron 2 of 10	5

Frequencies

GnomAD3 genomes AF: 0.00337 AC: 513 AN: 152126 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00394

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00118 AC: 296 AN: 251320 Hom.: 1 AF XY: 0.00105 AC XY: 142 AN XY: 135806

Gnomad AFR exome AF: 0.0114

Gnomad AMR exome AF: 0.000896

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00170

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000488 AC: 713 AN: 1461832 Hom.: 3 Cov.: 34 AF XY: 0.000491 AC XY: 357 AN XY: 727230

Gnomad4 AFR exome AF: 0.0112

Gnomad4 AMR exome AF: 0.000894

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000403

Gnomad4 SAS exome AF: 0.00154

Gnomad4 FIN exome AF: 0.000262

Gnomad4 NFE exome AF: 0.0000594

Gnomad4 OTH exome AF: 0.00108

GnomAD4 genome AF: 0.00337 AC: 513 AN: 152244 Hom.: 2 Cov.: 32 AF XY: 0.00344 AC XY: 256 AN XY: 74440

Gnomad4 AFR AF: 0.0111

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.000792 Hom.: 2

Bravo AF: 0.00365

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jun 02, 2015

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Oct 24, 2018

Labcorp Genetics (formerly Invitae), Labcorp

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	-0.83
CADD	Benign	0.0060
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000032
dbscSNV1_RF	Benign	0.0040
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: rs34613390; hg19: chr17-10318897;