Variant 12-57244331-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_145064.3(STAC3):c.842A>G(p.Asn281Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00101 in 1,614,140 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 5 hom. )

Consequence

STAC3
NM_145064.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.03

Variant links:

Genes affected

STAC3 (HGNC:28423): (SH3 and cysteine rich domain 3) The protein encoded by this gene is a component of the excitation-contraction coupling machinery of muscles. This protein is a member of the Stac gene family and contains an N-terminal cysteine-rich domain and two SH3 domains. Mutations in this gene are a cause of Native American myopathy. [provided by RefSeq, Nov 2013]

STAC3 links:

STAC3 (HGNC:):

STAC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010758579).

BP6

Variant 12-57244331-T-C is Benign according to our data. Variant chr12-57244331-T-C is described in ClinVar as [Benign]. Clinvar id is 262577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00404 (616/152288) while in subpopulation AFR AF= 0.0138 (573/41560). AF 95% confidence interval is 0.0129. There are 2 homozygotes in gnomad4. There are 312 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAC3	NM_145064.3 linkuse as main transcript	c.842A>G	p.Asn281Ser	missense_variant	10/12	ENST00000332782.7	NP_659501.1	Q96MF2-1A0A024RB38

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
STAC3	ENST00000332782.7 linkuse as main transcript	c.842A>G	p.Asn281Ser	missense_variant	10/12	2	NM_145064.3	ENSP00000329200.2	Q96MF2-1
STAC3	ENST00000554578.5 linkuse as main transcript	c.725A>G	p.Asn242Ser	missense_variant	9/11	1		ENSP00000452068.1	Q96MF2-2
STAC3	ENST00000557176.5 linkuse as main transcript	n.217A>G		non_coding_transcript_exon_variant	6/8	1		ENSP00000450740.1	G3V2L9
STAC3	ENST00000546246.2 linkuse as main transcript	c.284A>G	p.Asn95Ser	missense_variant	7/9	2		ENSP00000441515.2	Q96MF2-3

Frequencies

GnomAD3 genomes

AF:

0.00404

AC:

615

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000915

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00127

AC:

319

AN:

251392

Hom.:

AF XY:

0.00105

AC XY:

142

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.0142

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000501

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000695

AC:

1016

AN:

1461852

Hom.:

Cov.:

AF XY:

0.000650

AC XY:

473

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0149

Gnomad4 AMR exome

AF:

0.000402

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000375

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.00404

AC:

616

AN:

152288

Hom.:

Cov.:

AF XY:

0.00419

AC XY:

312

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0138

Gnomad4 AMR

AF:

0.000914

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000599

Hom.:

Bravo

AF:

0.00458

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00163

AC:

198

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Bailey-Bloch congenital myopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

.;T;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.98

D;D;D

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L;.

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.7

D;D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.013

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.64

MVP

0.64

MPC

0.95

ClinPred

0.020

GERP RS

5.4

Varity_R

0.59

gMVP

0.39

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