rs113470661

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005379.4(MYO1A):c.2390C>T(p.Ser797Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00599 in 1,614,148 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0049 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 32 hom. )

Consequence

MYO1A
NM_005379.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 8.02

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0073539317).

BP6

Variant 12-57031134-G-A is Benign according to our data. Variant chr12-57031134-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 178620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-57031134-G-A is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 742 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1A	NM_005379.4 link	c.2390C>T	p.Ser797Phe	missense_variant	Exon 23 of 28	ENST00000300119.8	NP_005370.1	Q9UBC5
MYO1A	NM_001256041.2 link	c.2390C>T	p.Ser797Phe	missense_variant	Exon 24 of 29		NP_001242970.1	Q9UBC5B2R643
MYO1A	XM_047428876.1 link	c.2390C>T	p.Ser797Phe	missense_variant	Exon 24 of 29		XP_047284832.1
MYO1A	XM_011538373.3 link	c.2390C>T	p.Ser797Phe	missense_variant	Exon 23 of 25		XP_011536675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1A	ENST00000300119.8 link	c.2390C>T	p.Ser797Phe	missense_variant	Exon 23 of 28	1	NM_005379.4	ENSP00000300119.3		Q9UBC5

Frequencies

GnomAD3 genomes

AF:

0.00488

AC:

742

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00838

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00839

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00451

AC:

1135

AN:

251450

Hom.:

AF XY:

0.00433

AC XY:

588

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00278

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000555

Gnomad FIN exome

AF:

0.00868

Gnomad NFE exome

AF:

0.00711

Gnomad OTH exome

AF:

0.00505

GnomAD4 exome

AF:

0.00611

AC:

8931

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00600

AC XY:

4367

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000806

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00218

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000487

Gnomad4 FIN exome

AF:

0.00796

Gnomad4 NFE exome

AF:

0.00716

Gnomad4 OTH exome

AF:

0.00576

GnomAD4 genome

AF:

0.00487

AC:

742

AN:

152268

Hom.:

Cov.:

AF XY:

0.00479

AC XY:

357

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00838

Gnomad4 NFE

AF:

0.00839

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00683

Hom.:

Bravo

AF:

0.00374

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00733

AC:

ExAC

AF:

0.00466

AC:

566

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00785

EpiControl

AF:

0.00575

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Ser797Phe in Exon 23 of MYO1A: This variant is not expected to have clinical sig nificance because it has been identified in 0.7% (47/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs113470661). -

Jul 30, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 01, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Feb 23, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24875298, 25262649, 24616153, 12736868) -

Dec 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MYO1A: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Pathogenic

0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;T

Eigen

Benign

0.16

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.79

.;T

MetaRNN

Benign

0.0074

T;T

MetaSVM

Uncertain

0.19

MutationAssessor

Pathogenic

2.9

M;M

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-4.1

D;D

REVEL

Pathogenic

0.67

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.44

B;B

Vest4

0.43

MVP

0.86

MPC

0.32

ClinPred

0.045

GERP RS

4.2

Varity_R

0.32

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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