Variant 12-57029219-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_005379.4(MYO1A):c.2918G>A(p.Ser973Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S973S) has been classified as Benign.

Frequency

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

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

MYO1A
NM_005379.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.64

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MYO1A	NM_005379.4 linkuse as main transcript	c.2918G>A	p.Ser973Asn	missense_variant	27/28	ENST00000300119.8
MYO1A	NM_001256041.2 linkuse as main transcript	c.2918G>A	p.Ser973Asn	missense_variant	28/29
MYO1A	XM_047428876.1 linkuse as main transcript	c.2918G>A	p.Ser973Asn	missense_variant	28/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MYO1A	ENST00000300119.8 linkuse as main transcript	c.2918G>A	p.Ser973Asn	missense_variant	27/28	1	NM_005379.4	P1
MYO1A	ENST00000442789.6 linkuse as main transcript	c.2918G>A	p.Ser973Asn	missense_variant	28/29	1		P1
MYO1A	ENST00000554234.5 linkuse as main transcript	c.*363G>A		3_prime_UTR_variant, NMD_transcript_variant	23/24	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 13, 2022

The c.2918G>A (p.S973N) alteration is located in exon 27 (coding exon 26) of the MYO1A gene. This alteration results from a G to A substitution at nucleotide position 2918, causing the serine (S) at amino acid position 973 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.086

T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.97

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.74

D;D

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.8

M;M

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.26

Sift

Benign

0.081

T;T

Sift4G

Benign

0.16

T;T

Polyphen

1.0

D;D

Vest4

0.56

MutPred

0.64

Gain of catalytic residue at S973 (P = 0.0067);Gain of catalytic residue at S973 (P = 0.0067);

MVP

0.67

MPC

0.43

ClinPred

0.99

GERP RS

4.2

Varity_R

0.20

gMVP

0.43

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