Variant chr12-57029584-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000300119.8(MYO1A):c.2728T>C(p.Ser910Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

MYO1A
ENST00000300119.8 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.34

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.956

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MYO1A	NM_005379.4 linkuse as main transcript	c.2728T>C	p.Ser910Pro	missense_variant	26/28	ENST00000300119.8	NP_005370.1
MYO1A	NM_001256041.2 linkuse as main transcript	c.2728T>C	p.Ser910Pro	missense_variant	27/29		NP_001242970.1
MYO1A	XM_047428876.1 linkuse as main transcript	c.2728T>C	p.Ser910Pro	missense_variant	27/29		XP_047284832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MYO1A	ENST00000300119.8 linkuse as main transcript	c.2728T>C	p.Ser910Pro	missense_variant	26/28	1	NM_005379.4	ENSP00000300119	P1
MYO1A	ENST00000442789.6 linkuse as main transcript	c.2728T>C	p.Ser910Pro	missense_variant	27/29	1		ENSP00000393392	P1
MYO1A	ENST00000477864.1 linkuse as main transcript	n.291T>C		non_coding_transcript_exon_variant	4/4	2
MYO1A	ENST00000554234.5 linkuse as main transcript	c.*173T>C		3_prime_UTR_variant, NMD_transcript_variant	22/24	5		ENSP00000451033

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

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

Uncertain

0.42

BayesDel_addAF

Uncertain

0.048

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;T

Eigen

Benign

0.16

Eigen_PC

Benign

0.057

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.040

MetaRNN

Pathogenic

0.96

D;D

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.7

M;M

MutationTaster

Benign

0.000019

A;A;A

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.4

N;N

REVEL

Uncertain

0.29

Sift

Benign

0.13

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.96

D;D

Vest4

0.49

MutPred

0.85

Gain of sheet (P = 4e-04);Gain of sheet (P = 4e-04);

MVP

0.67

MPC

0.38

ClinPred

0.92

GERP RS

3.3

Varity_R

0.38

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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