Variant chr17-10391659-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_002472.3(MYH8):c.5664+223C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,104 control chromosomes in the GnomAD database, including 2,875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.17 ( 2875 hom., cov: 32)

Consequence

MYH8
NM_002472.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.07

Variant links:

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]

MYH8 links:

ENSG00000272736 (HGNC:):

ENSG00000272736 links:

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]

MYHAS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP6

Variant 17-10391659-G-A is Benign according to our data. Variant chr17-10391659-G-A is described in ClinVar as [Benign]. Clinvar id is 1178307.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH8	NM_002472.3 link	c.5664+223C>T		intron_variant		ENST00000403437.2	NP_002463.2	P13535
MYHAS	NR_125367.1 link	n.76+8452G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MYH8	ENST00000403437.2 link	c.5664+223C>T	intron_variant	5	NM_002472.3	ENSP00000384330.2	P13535
ENSG00000272736	ENST00000399342.6 link	n.76+8452G>A	intron_variant	3
ENSG00000272736	ENST00000581304.1 link	n.52+8452G>A	intron_variant	3
MYHAS	ENST00000587182.2 link	n.64+8452G>A	intron_variant	5

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25489

AN:

151986

Hom.:

2876

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0495

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0707

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.249

Gnomad OTH

AF:

0.197

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.168

AC:

25487

AN:

152104

Hom.:

2875

Cov.:

AF XY:

0.163

AC XY:

12117

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0494

Gnomad4 AMR

AF:

0.157

Gnomad4 ASJ

AF:

0.260

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0708

Gnomad4 FIN

AF:

0.203

Gnomad4 NFE

AF:

0.249

Gnomad4 OTH

AF:

0.196

Alfa

AF:

0.204

Hom.:

442

Bravo

AF:

0.163

Asia WGS

AF:

0.0420

AC:

148

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

-1.0

CADD

Benign

0.13

DANN

Benign

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over