rs12601552

chr17-10411058-G-Achr17-10411058-G-Cchr17-10411058-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002472.3(MYH8):c.1417-111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 1,553,184 control chromosomes in the GnomAD database, including 128,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (12118 hom., cov: 32)
  • Exomes 𝑓: 0.39 (116370 hom.)
• Consequence: MYH8 NM_002472.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.26

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 17-10411058-G-A is Benign according to our data. Variant chr17-10411058-G-A is described in ClinVar as [Benign]. Clinvar id is 1181307.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH8	NM_002472.3	c.1417-111C>T		intron_variant		ENST00000403437.2
MYHAS	NR_125367.1	n.167+4820G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH8	ENST00000403437.2	c.1417-111C>T		intron_variant		5	NM_002472.3	P1
	ENST00000399342.6	n.206+4781G>A		intron_variant, non_coding_transcript_variant		3
	ENST00000581304.1	n.143+4820G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57577 AN: 151830 Hom.: 12109 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.867

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.367

GnomAD4 exome AF: 0.392 AC: 549394 AN: 1401236 Hom.: 116370 AF XY: 0.398 AC XY: 277141 AN XY: 696248

Gnomad4 AFR exome AF: 0.269

Gnomad4 AMR exome AF: 0.563

Gnomad4 ASJ exome AF: 0.403

Gnomad4 EAS exome AF: 0.847

Gnomad4 SAS exome AF: 0.612

Gnomad4 FIN exome AF: 0.424

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.408

GnomAD4 genome AF: 0.379 AC: 57623 AN: 151948 Hom.: 12118 Cov.: 32 AF XY: 0.393 AC XY: 29184 AN XY: 74246

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.866

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.359

Gnomad4 OTH AF: 0.369

Alfa AF: 0.357 Hom.: 1221

Bravo AF: 0.373

Asia WGS AF: 0.712 AC: 2472 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.21
Dann	Benign	0.48

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: rs12601552; hg19: chr17-10314375;