12-57047357-C-T

Position:

chr12-57047357-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005379.4(MYO1A):c.376G>A(p.Glu126Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00118 in 1,614,194 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 6 hom. )

Consequence

MYO1A
NM_005379.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.48

Variant links:

Genes affected

MYO1A (HGNC:7595): (myosin IA) This gene encodes a member of the myosin superfamily. The protein represents an unconventional myosin; it should not be confused with the conventional skeletal muscle myosin-1 (MYH1). Unconventional myosins contain the basic domains characteristic of conventional myosins and are further distinguished from class members by their tail domains. They function as actin-based molecular motors. Mutations in this gene have been associated with autosomal dominant deafness. Alternatively spliced variants have been found for this gene. [provided by RefSeq, Dec 2011]

MYO1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.055823).

BP6

Variant 12-57047357-C-T is Benign according to our data. Variant chr12-57047357-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 178456.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 82 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MYO1A	NM_005379.4 linkuse as main transcript	c.376G>A	p.Glu126Lys	missense_variant	5/28	ENST00000300119.8
MYO1A	NM_001256041.2 linkuse as main transcript	c.376G>A	p.Glu126Lys	missense_variant	6/29
MYO1A	XM_047428876.1 linkuse as main transcript	c.376G>A	p.Glu126Lys	missense_variant	6/29
MYO1A	XM_011538373.3 linkuse as main transcript	c.376G>A	p.Glu126Lys	missense_variant	5/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MYO1A	ENST00000300119.8 linkuse as main transcript	c.376G>A	p.Glu126Lys	missense_variant	5/28	1	NM_005379.4	P1
MYO1A	ENST00000442789.6 linkuse as main transcript	c.376G>A	p.Glu126Lys	missense_variant	6/29	1		P1
MYO1A	ENST00000492945.5 linkuse as main transcript	c.-21+2530G>A		intron_variant		4
MYO1A	ENST00000554234.5 linkuse as main transcript	c.-64G>A		5_prime_UTR_variant, NMD_transcript_variant	2/24	5

Frequencies

GnomAD3 genomes

AF:

0.000539

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000482

AC:

121

AN:

250812

Hom.:

AF XY:

0.000421

AC XY:

AN XY:

135528

show subpopulations

Gnomad AFR exome

AF:

0.000370

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000945

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.00125

AC:

1827

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

841

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00154

Gnomad4 OTH exome

AF:

0.00171

GnomAD4 genome

AF:

0.000538

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00106

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.000638

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000445

AC:

EpiCase

AF:

0.00147

EpiControl

AF:

0.000652

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Oct 04, 2014

p.Gly126Lys in exon 5 of MYO1A: This variant is not expected to have clinical si gnificance because it has been identified in 0.1% (10/8600) of European American chromosomes by the NHLBI Exome Sequencing Project and in 1.2% (2/170) of CEU (c aucasian) chromosomes by the 1000 Genomes Project (http://evs.gs.washington.edu/ EVS/; dbSNP rs151045364). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.86

.;D

M_CAP

Benign

0.040

MetaRNN

Benign

0.056

T;T

MetaSVM

Benign

-0.32

MutationAssessor

Benign

0.24

N;N

MutationTaster

Benign

0.66

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.1

N;N

REVEL

Uncertain

0.36

Sift

Benign

0.75

T;T

Sift4G

Benign

0.66

T;T

Polyphen

0.98

D;D

Vest4

0.38

MVP

0.85

MPC

0.11

ClinPred

0.041

GERP RS

5.2

Varity_R

0.12

gMVP

0.45

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