dbSNP rs12601552: MYH8:c.1417-111C>T (chr17-10411058-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.26

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 -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
MYH8	NM_002472.3 link	c.1417-111C>T		intron_variant	Intron 14 of 39	ENST00000403437.2	NP_002463.2	P13535
MYHAS	NR_125367.1 link	n.167+4820G>A		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYH8	ENST00000403437.2 link	c.1417-111C>T	intron_variant	Intron 14 of 39	5	NM_002472.3	ENSP00000384330.2	P13535
ENSG00000272736	ENST00000399342.6 link	n.206+4781G>A	intron_variant	Intron 2 of 3	3
ENSG00000272736	ENST00000581304.1 link	n.143+4820G>A	intron_variant	Intron 2 of 3	3
MYHAS	ENST00000587182.2 link	n.155+4820G>A	intron_variant	Intron 2 of 10	5

Frequencies

GnomAD3 genomes

AF:

0.379

AC:

57577

AN:

151830

Hom.:

12109

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.393

AC XY:

29184

AN XY:

74246

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

-0.98

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

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