Variant 12-56155129-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002475.5(MYL6B):c.277A>G(p.Met93Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000462 in 1,613,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 0 hom. )

Consequence

MYL6B
NM_002475.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86

Variant links:

Genes affected

MYL6B (HGNC:29823): (myosin light chain 6B) Myosin is a hexameric ATPase cellular motor protein. It is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatable regulatory light chains. This gene encodes a myosin alkali light chain expressed in both slow-twitch skeletal muscle and in nonmuscle tissue. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

MYL6B links:

MYL6B (HGNC:):

MYL6B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039673775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL6B	NM_002475.5 linkuse as main transcript	c.277A>G	p.Met93Val	missense_variant	4/8	ENST00000695999.1	NP_002466.1	P14649A0A024RB31
MYL6B	NM_001199629.2 linkuse as main transcript	c.277A>G	p.Met93Val	missense_variant	4/8		NP_001186558.1	P14649A0A024RB31
MYL6B-AS1	NR_186043.1 linkuse as main transcript	n.355+2505T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL6B	ENST00000695999.1 linkuse as main transcript	c.277A>G	p.Met93Val	missense_variant	4/8		NM_002475.5	ENSP00000512320.1		P14649

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000394

AC:

AN:

251324

Hom.:

AF XY:

0.000412

AC XY:

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00427

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000414

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000477

AC:

697

AN:

1461822

Hom.:

Cov.:

AF XY:

0.000473

AC XY:

344

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00482

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000479

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.000322

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000726

Hom.:

Bravo

AF:

0.000370

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000379

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.277A>G (p.M93V) alteration is located in exon 4 (coding exon 3) of the MYL6B gene. This alteration results from a A to G substitution at nucleotide position 277, causing the methionine (M) at amino acid position 93 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;T;.

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.85

.;D;T

M_CAP

Benign

0.065

MetaRNN

Benign

0.040

T;T;T

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.8

L;L;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.1

N;N;N

REVEL

Uncertain

0.53

Sift

Uncertain

0.025

D;D;D

Sift4G

Benign

0.092

T;T;D

Polyphen

0.81

P;P;.

Vest4

0.45

MVP

0.69

MPC

0.16

ClinPred

0.042

GERP RS

4.3

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.55

gMVP

0.76

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