Variant rs141278987 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002469.3(MYF6):c.544A>C(p.Thr182Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000484 in 1,576,370 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 2 hom. )

Consequence

MYF6
NM_002469.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.07

Variant links:

Genes affected

MYF6 (HGNC:7566): (myogenic factor 6) The protein encoded by this gene is a probable basic helix-loop-helix (bHLH) DNA binding protein involved in muscle differentiation. The encoded protein likely acts as a heterodimer with another bHLH protein. Defects in this gene are a cause of autosomal dominant centronuclear myopathy (ADCNM). [provided by RefSeq, May 2010]

MYF6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012334496).

BP6

Variant 12-80708548-A-C is Benign according to our data. Variant chr12-80708548-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 472757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 394 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYF6	NM_002469.3 linkuse as main transcript	c.544A>C	p.Thr182Pro	missense_variant	2/3	ENST00000228641.4	NP_002460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYF6	ENST00000228641.4 linkuse as main transcript	c.544A>C	p.Thr182Pro	missense_variant	2/3	1	NM_002469.3	ENSP00000228641	P1

Frequencies

GnomAD3 genomes

AF:

0.00264

AC:

391

AN:

148190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00918

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00107

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000229

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000970

GnomAD3 exomes

AF:

0.000672

AC:

169

AN:

251476

Hom.:

AF XY:

0.000493

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00911

Gnomad AMR exome

AF:

0.000520

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000258

AC:

369

AN:

1428048

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

165

AN XY:

710530

show subpopulations

Gnomad4 AFR exome

AF:

0.00980

Gnomad4 AMR exome

AF:

0.000572

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000275

Gnomad4 OTH exome

AF:

0.000361

GnomAD4 genome

AF:

0.00266

AC:

394

AN:

148322

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

187

AN XY:

72442

show subpopulations

Gnomad4 AFR

AF:

0.00925

Gnomad4 AMR

AF:

0.00107

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000961

Alfa

AF:

0.000759

Hom.:

Bravo

AF:

0.00301

ExAC

AF:

0.000684

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal dominant centronuclear myopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 07, 2023

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

MYF6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Pathogenic

0.21

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.18

Eigen

Benign

0.016

Eigen_PC

Benign

0.0019

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.50

MetaRNN

Benign

0.012

MetaSVM

Uncertain

0.44

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.23

REVEL

Pathogenic

0.67

Sift

Uncertain

0.018

Sift4G

Benign

0.21

Polyphen

0.92

Vest4

0.59

MVP

0.99

MPC

0.95

ClinPred

0.029

GERP RS

4.2

Varity_R

0.21

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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