12-57029150-G-A

Position:

chr12-57029150-G-A

Variant summary

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

The NM_005379.4(MYO1A):c.2987C>T(p.Thr996Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0855 in 1,613,994 control chromosomes in the GnomAD database, including 6,213 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.090 ( 646 hom., cov: 31)

Exomes 𝑓: 0.085 ( 5567 hom. )

Consequence

MYO1A
NM_005379.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.23

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=0.0014393628).

BP6

Variant 12-57029150-G-A is Benign according to our data. Variant chr12-57029150-G-A is described in ClinVar as [Benign]. Clinvar id is 45311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-57029150-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.172 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.2987C>T	p.Thr996Ile	missense_variant	27/28	ENST00000300119.8	NP_005370.1
MYO1A	NM_001256041.2 linkuse as main transcript	c.2987C>T	p.Thr996Ile	missense_variant	28/29		NP_001242970.1
MYO1A	XM_047428876.1 linkuse as main transcript	c.2987C>T	p.Thr996Ile	missense_variant	28/29		XP_047284832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MYO1A	ENST00000300119.8 linkuse as main transcript	c.2987C>T	p.Thr996Ile	missense_variant	27/28	1	NM_005379.4	ENSP00000300119	P1
MYO1A	ENST00000442789.6 linkuse as main transcript	c.2987C>T	p.Thr996Ile	missense_variant	28/29	1		ENSP00000393392	P1
MYO1A	ENST00000554234.5 linkuse as main transcript	c.*432C>T		3_prime_UTR_variant, NMD_transcript_variant	23/24	5		ENSP00000451033

Frequencies

GnomAD3 genomes

AF:

0.0897

AC:

13632

AN:

152018

Hom.:

647

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0792

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.0746

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.105

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0810

Gnomad OTH

AF:

0.0820

GnomAD3 exomes

AF:

0.0952

AC:

23903

AN:

251188

Hom.:

1281

AF XY:

0.0950

AC XY:

12902

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.0804

Gnomad AMR exome

AF:

0.0881

Gnomad ASJ exome

AF:

0.0763

Gnomad EAS exome

AF:

0.186

Gnomad SAS exome

AF:

0.0992

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.0841

Gnomad OTH exome

AF:

0.0883

GnomAD4 exome

AF:

0.0851

AC:

124358

AN:

1461858

Hom.:

5567

Cov.:

AF XY:

0.0850

AC XY:

61804

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0804

Gnomad4 AMR exome

AF:

0.0904

Gnomad4 ASJ exome

AF:

0.0742

Gnomad4 EAS exome

AF:

0.139

Gnomad4 SAS exome

AF:

0.100

Gnomad4 FIN exome

AF:

0.102

Gnomad4 NFE exome

AF:

0.0813

Gnomad4 OTH exome

AF:

0.0851

GnomAD4 genome

AF:

0.0896

AC:

13637

AN:

152136

Hom.:

646

Cov.:

AF XY:

0.0924

AC XY:

6869

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0791

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.0746

Gnomad4 EAS

AF:

0.181

Gnomad4 SAS

AF:

0.105

Gnomad4 FIN

AF:

0.104

Gnomad4 NFE

AF:

0.0810

Gnomad4 OTH

AF:

0.0835

Alfa

AF:

0.0849

Hom.:

1294

Bravo

AF:

0.0891

TwinsUK

AF:

0.0771

AC:

286

ALSPAC

AF:

0.0786

AC:

303

ESP6500AA

AF:

0.0856

AC:

377

ESP6500EA

AF:

0.0852

AC:

733

ExAC

AF:

0.0944

AC:

11462

Asia WGS

AF:

0.133

AC:

460

AN:

3478

EpiCase

AF:

0.0773

EpiControl

AF:

0.0722

ClinVar

Significance: Benign

Submissions summary: Benign: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	May 09, 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	May 07, 2012	Thr996Ile in Exon 27 of MYO1A: This variant is not expected to have clinical sig nificance because it has been identified in 8.6% (605/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs17119344). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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

0.096

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.067

T;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.10

.;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.029

Sift

Benign

0.20

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.029

B;B

Vest4

0.076

MPC

0.088

ClinPred

0.0044

GERP RS

4.1

Varity_R

0.075

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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