chr12-57037571-T-A

Variant names:

Variant summary

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

The NM_005379.4(MYO1A):c.2032A>T(p.Ile678Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,614,146 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 20 hom. )

Consequence

MYO1A
NM_005379.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:4

Conservation

PhyloP100: 1.60

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.045950323).

BP6

Variant 12-57037571-T-A is Benign according to our data. Variant chr12-57037571-T-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 164588.We mark this variant Likely_benign, oryginal submissions are: {Benign=4, Uncertain_significance=1}. Variant chr12-57037571-T-A is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 397 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1A	NM_005379.4 link	c.2032A>T	p.Ile678Phe	missense_variant	Exon 19 of 28	ENST00000300119.8	NP_005370.1	Q9UBC5
MYO1A	NM_001256041.2 link	c.2032A>T	p.Ile678Phe	missense_variant	Exon 20 of 29		NP_001242970.1	Q9UBC5B2R643
MYO1A	XM_047428876.1 link	c.2032A>T	p.Ile678Phe	missense_variant	Exon 20 of 29		XP_047284832.1
MYO1A	XM_011538373.3 link	c.2032A>T	p.Ile678Phe	missense_variant	Exon 19 of 25		XP_011536675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO1A	ENST00000300119.8 link	c.2032A>T	p.Ile678Phe	missense_variant	Exon 19 of 28	1	NM_005379.4	ENSP00000300119.3	Q9UBC5
MYO1A	ENST00000442789.6 link	c.2032A>T	p.Ile678Phe	missense_variant	Exon 20 of 29	1		ENSP00000393392.2	Q9UBC5
MYO1A	ENST00000554234.5 link	n.1546A>T		non_coding_transcript_exon_variant	Exon 15 of 24	5		ENSP00000451033.1	G3V342

Frequencies

GnomAD3 genomes

AF:

0.00260

AC:

395

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.0104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00269

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00302

AC:

757

AN:

251046

Hom.:

AF XY:

0.00346

AC XY:

470

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.000801

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.00378

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00559

Gnomad FIN exome

AF:

0.00864

Gnomad NFE exome

AF:

0.00267

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00316

AC:

4613

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00327

AC XY:

2378

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.00417

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00585

Gnomad4 FIN exome

AF:

0.00730

Gnomad4 NFE exome

AF:

0.00302

Gnomad4 OTH exome

AF:

0.00298

GnomAD4 genome

AF:

0.00261

AC:

397

AN:

152288

Hom.:

Cov.:

AF XY:

0.00295

AC XY:

220

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.0104

Gnomad4 NFE

AF:

0.00270

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00229

Hom.:

Bravo

AF:

0.00213

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00290

AC:

352

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00174

EpiControl

AF:

0.00302

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 20, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 20, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ile678Phe in exon 19 of MYO1A: This variant is not expected to have clinical sig nificance because it has been identified in 0.3% (27/8573) of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/ EVS/; dbSNP rs151269703). -

not provided

Benign:2

May 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

DIARRHEA 15, CONGENITAL

Pathogenic:1

Apr 16, 2025

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Congenital diarrhea

Uncertain:1

Jul 02, 2024

Aleixo Muise Laboratory, Hospital For Sick Children

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Pathogenic

0.19

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.81

D;D

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.87

LIST_S2

Pathogenic

0.99

.;D

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.046

T;T

MetaSVM

Uncertain

0.46

MutationAssessor

Pathogenic

3.9

H;H

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.6

D;D

REVEL

Pathogenic

0.84

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.94

P;P

Vest4

0.89

MVP

0.83

MPC

0.54

ClinPred

0.044

GERP RS

2.6

Varity_R

0.92

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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