Variant 12-80707798-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_002469.3(MYF6):c.79G>A(p.Val27Met) variant causes a missense change. The variant allele was found at a frequency of 0.00045 in 1,614,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00047 ( 0 hom. )

Consequence

MYF6
NM_002469.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 3.79

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.034634143).

BP6

Variant 12-80707798-G-A is Benign according to our data. Variant chr12-80707798-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 658350.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High AC in GnomAd at 43 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYF6	NM_002469.3 linkuse as main transcript	c.79G>A	p.Val27Met	missense_variant	1/3	ENST00000228641.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYF6	ENST00000228641.4 linkuse as main transcript	c.79G>A	p.Val27Met	missense_variant	1/3	1	NM_002469.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000398

AC:

100

AN:

251490

Hom.:

AF XY:

0.000390

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000835

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000467

AC:

683

AN:

1461874

Hom.:

Cov.:

AF XY:

0.000436

AC XY:

317

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.000584

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000282

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000490

Hom.:

Bravo

AF:

0.000249

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000552

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.79G>A (p.V27M) alteration is located in exon 1 (coding exon 1) of the MYF6 gene. This alteration results from a G to A substitution at nucleotide position 79, causing the valine (V) at amino acid position 27 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Autosomal dominant centronuclear myopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.40

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.26

Eigen

Benign

-0.23

Eigen_PC

Benign

0.032

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0062

MetaRNN

Benign

0.035

MetaSVM

Benign

-0.88

MutationAssessor

Benign

-0.32

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.35

REVEL

Benign

0.16

Sift

Benign

0.088

Sift4G

Benign

0.21

Polyphen

0.0010

Vest4

0.069

MVP

0.83

MPC

0.37

ClinPred

0.042

GERP RS

4.6

Varity_R

0.090

gMVP

0.20

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