12-57029218-G-A

Position:

chr12-57029218-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_005379.4(MYO1A):c.2919C>T(p.Ser973=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,614,060 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 30 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 29 hom. )

Consequence

MYO1A
NM_005379.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.628

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 12-57029218-G-A is Benign according to our data. Variant chr12-57029218-G-A is described in ClinVar as [Benign]. Clinvar id is 164578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.628 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0108 (1638/152188) while in subpopulation AFR AF= 0.0367 (1523/41494). AF 95% confidence interval is 0.0352. There are 30 homozygotes in gnomad4. There are 795 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1638 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MYO1A	NM_005379.4 linkuse as main transcript	c.2919C>T	p.Ser973=	synonymous_variant	27/28	ENST00000300119.8	NP_005370.1
MYO1A	NM_001256041.2 linkuse as main transcript	c.2919C>T	p.Ser973=	synonymous_variant	28/29		NP_001242970.1
MYO1A	XM_047428876.1 linkuse as main transcript	c.2919C>T	p.Ser973=	synonymous_variant	28/29		XP_047284832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MYO1A	ENST00000300119.8 linkuse as main transcript	c.2919C>T	p.Ser973=	synonymous_variant	27/28	1	NM_005379.4	ENSP00000300119	P1
MYO1A	ENST00000442789.6 linkuse as main transcript	c.2919C>T	p.Ser973=	synonymous_variant	28/29	1		ENSP00000393392	P1
MYO1A	ENST00000554234.5 linkuse as main transcript	c.*364C>T		3_prime_UTR_variant, NMD_transcript_variant	23/24	5		ENSP00000451033

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1628

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0365

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00550

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00909

GnomAD3 exomes

AF:

0.00280

AC:

702

AN:

251046

Hom.:

AF XY:

0.00204

AC XY:

277

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.0375

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00119

AC:

1739

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

758

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0397

Gnomad4 AMR exome

AF:

0.00201

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000854

Gnomad4 OTH exome

AF:

0.00320

GnomAD4 genome

AF:

0.0108

AC:

1638

AN:

152188

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

795

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0367

Gnomad4 AMR

AF:

0.00550

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.00505

Hom.:

Bravo

AF:

0.0124

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

May 07, 2012

Ser973Ser in Exon 27 of MYO1A: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 3.9% (147/3738) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs79857347). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.2

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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