rs33962952

Positions:

chr12-57037618-C-T

Variant summary

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

The NM_005379.4(MYO1A):c.1985G>A(p.Gly662Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 1,614,020 control chromosomes in the GnomAD database, including 869 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 68 hom., cov: 32)

Exomes 𝑓: 0.029 ( 801 hom. )

Consequence

MYO1A
NM_005379.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:4

Conservation

PhyloP100: -1.80

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009011149).

BP6

Variant 12-57037618-C-T is Benign according to our data. Variant chr12-57037618-C-T is described in ClinVar as [Benign]. Clinvar id is 8150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-57037618-C-T is described in Lovd as [Benign]. Variant chr12-57037618-C-T is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MYO1A	NM_005379.4 linkuse as main transcript	c.1985G>A	p.Gly662Glu	missense_variant	19/28	ENST00000300119.8	NP_005370.1
MYO1A	NM_001256041.2 linkuse as main transcript	c.1985G>A	p.Gly662Glu	missense_variant	20/29		NP_001242970.1
MYO1A	XM_047428876.1 linkuse as main transcript	c.1985G>A	p.Gly662Glu	missense_variant	20/29		XP_047284832.1
MYO1A	XM_011538373.3 linkuse as main transcript	c.1985G>A	p.Gly662Glu	missense_variant	19/25		XP_011536675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MYO1A	ENST00000300119.8 linkuse as main transcript	c.1985G>A	p.Gly662Glu	missense_variant	19/28	1	NM_005379.4	ENSP00000300119	P1
MYO1A	ENST00000442789.6 linkuse as main transcript	c.1985G>A	p.Gly662Glu	missense_variant	20/29	1		ENSP00000393392	P1
MYO1A	ENST00000554234.5 linkuse as main transcript	c.1499G>A	p.Gly500Glu	missense_variant, NMD_transcript_variant	15/24	5		ENSP00000451033

Frequencies

GnomAD3 genomes

AF:

0.0240

AC:

3647

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00473

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0194

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0170

Gnomad FIN

AF:

0.0336

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0326

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0298

AC:

7473

AN:

250634

Hom.:

169

AF XY:

0.0313

AC XY:

4246

AN XY:

135530

show subpopulations

Gnomad AFR exome

AF:

0.00396

Gnomad AMR exome

AF:

0.0195

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0237

Gnomad FIN exome

AF:

0.0320

Gnomad NFE exome

AF:

0.0349

Gnomad OTH exome

AF:

0.0416

GnomAD4 exome

AF:

0.0289

AC:

42190

AN:

1461752

Hom.:

801

Cov.:

AF XY:

0.0292

AC XY:

21216

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.00481

Gnomad4 AMR exome

AF:

0.0195

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0228

Gnomad4 FIN exome

AF:

0.0319

Gnomad4 NFE exome

AF:

0.0291

Gnomad4 OTH exome

AF:

0.0325

GnomAD4 genome

AF:

0.0239

AC:

3644

AN:

152268

Hom.:

Cov.:

AF XY:

0.0236

AC XY:

1757

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00469

Gnomad4 AMR

AF:

0.0194

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0174

Gnomad4 FIN

AF:

0.0336

Gnomad4 NFE

AF:

0.0326

Gnomad4 OTH

AF:

0.0303

Alfa

AF:

0.0348

Hom.:

155

Bravo

AF:

0.0226

TwinsUK

AF:

0.0237

AC:

ALSPAC

AF:

0.0293

AC:

113

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.0377

AC:

324

ExAC

AF:

0.0300

AC:

3642

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.0415

EpiControl

AF:

0.0419

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 09, 2013	This variant has been identified in 3.8% (324/8600) of European American chromos omes from a broad population by the NHLBI Exome Sequencing Project (http://evs.g s.washington.edu/EVS/; dbSNP rs33962952) -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Autosomal dominant nonsyndromic hearing loss 48

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

May 01, 2014

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.50

CADD

Benign

1.7

DANN

Benign

0.57

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.53

.;T

MetaRNN

Benign

0.0090

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.0

N;N

MutationTaster

Benign

0.097

A;A;A

PrimateAI

Benign

0.32

PROVEAN

Benign

1.5

N;N

REVEL

Benign

0.064

Sift

Benign

1.0

T;T

Sift4G

Benign

0.94

T;T

Polyphen

0.0010

B;B

Vest4

0.15

MPC

0.11

ClinPred

0.0037

GERP RS

-1.1

Varity_R

0.084

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

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