rs55679042

Positions:

chr12-57043335-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_005379.4(MYO1A):c.916G>A(p.Val306Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00789 in 1,614,104 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 41 hom. )

Consequence

MYO1A
NM_005379.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1B:5

Conservation

PhyloP100: 0.205

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.110271215).

BP6

Variant 12-57043335-C-T is Benign according to our data. Variant chr12-57043335-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 8148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-57043335-C-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 838 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MYO1A	NM_005379.4 linkuse as main transcript	c.916G>A	p.Val306Met	missense_variant	11/28	ENST00000300119.8	NP_005370.1
MYO1A	NM_001256041.2 linkuse as main transcript	c.916G>A	p.Val306Met	missense_variant	12/29		NP_001242970.1
MYO1A	XM_047428876.1 linkuse as main transcript	c.916G>A	p.Val306Met	missense_variant	12/29		XP_047284832.1
MYO1A	XM_011538373.3 linkuse as main transcript	c.916G>A	p.Val306Met	missense_variant	11/25		XP_011536675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MYO1A	ENST00000300119.8 linkuse as main transcript	c.916G>A	p.Val306Met	missense_variant	11/28	1	NM_005379.4	ENSP00000300119	P1
MYO1A	ENST00000442789.6 linkuse as main transcript	c.916G>A	p.Val306Met	missense_variant	12/29	1		ENSP00000393392	P1
MYO1A	ENST00000492945.5 linkuse as main transcript	c.4G>A	p.Val2Met	missense_variant	3/5	4		ENSP00000452229
MYO1A	ENST00000554234.5 linkuse as main transcript	c.430G>A	p.Val144Met	missense_variant, NMD_transcript_variant	7/24	5		ENSP00000451033

Frequencies

GnomAD3 genomes

AF:

0.00551

AC:

838

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00942

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00545

AC:

1369

AN:

251324

Hom.:

AF XY:

0.00544

AC XY:

739

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00289

Gnomad ASJ exome

AF:

0.00457

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00170

Gnomad FIN exome

AF:

0.00245

Gnomad NFE exome

AF:

0.00931

Gnomad OTH exome

AF:

0.00490

GnomAD4 exome

AF:

0.00814

AC:

11898

AN:

1461804

Hom.:

Cov.:

AF XY:

0.00788

AC XY:

5731

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.00176

Gnomad4 AMR exome

AF:

0.00331

Gnomad4 ASJ exome

AF:

0.00459

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.00195

Gnomad4 FIN exome

AF:

0.00294

Gnomad4 NFE exome

AF:

0.00975

Gnomad4 OTH exome

AF:

0.00639

GnomAD4 genome

AF:

0.00550

AC:

838

AN:

152300

Hom.:

Cov.:

AF XY:

0.00512

AC XY:

381

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.00942

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00838

Hom.:

Bravo

AF:

0.00554

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00965

AC:

ExAC

AF:

0.00553

AC:

672

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00862

EpiControl

AF:

0.00818

ClinVar

Significance: Benign/Likely benign

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 04, 2018	This variant is associated with the following publications: (PMID: 27759032, 25262649, 24616153, 25333069, 12736868) -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	MYO1A: BP4, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jul 16, 2013	Val306Met in exon 11 of MYO1A: This variant is not expected to have clinical sig nificance because it has been identified in 1% (83/8600) of European American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS/; dbSNP rs55679042) and due to a lack of conservation across species, including mammals. Of note, at least 6 different mammals (rat, mouse, tree shrew, pika, microbat, and wallaby) have a Methionine (Met) at this position despite high nearby amino acid conservation. -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 21, 2014	- -

Autosomal dominant nonsyndromic hearing loss 48

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

May 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.12

CADD

Benign

8.2

DANN

Benign

0.76

DEOGEN2

Benign

0.18

T;T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.71

.;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

-1.1

N;N;.

MutationTaster

Benign

0.0013

A;A;A

PrimateAI

Benign

0.28

PROVEAN

Benign

0.17

N;N;N

REVEL

Uncertain

0.49

Sift

Benign

0.15

T;T;T

Sift4G

Uncertain

0.045

D;D;.

Polyphen

0.0060

B;B;.

Vest4

0.14

MVP

0.60

MPC

0.088

ClinPred

0.0013

GERP RS

-1.2

Varity_R

0.066

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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