Variant 12-57245219-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_145064.3(STAC3):c.604-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00933 in 1,613,798 control chromosomes in the GnomAD database, including 208 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0094 ( 186 hom. )

Consequence

STAC3
NM_145064.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0008489

Clinical Significance

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

Conservation

PhyloP100: 3.14

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 12-57245219-G-A is Benign according to our data. Variant chr12-57245219-G-A is described in ClinVar as [Benign]. Clinvar id is 262576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAC3	NM_145064.3 linkuse as main transcript	c.604-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000332782.7	NP_659501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAC3	ENST00000332782.7 linkuse as main transcript	c.604-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_145064.3	ENSP00000329200	P1	Q96MF2-1

Frequencies

GnomAD3 genomes

AF:

0.00891

AC:

1355

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00908

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.0719

Gnomad SAS

AF:

0.0213

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00657

Gnomad OTH

AF:

0.00575

GnomAD3 exomes

AF:

0.0109

AC:

2737

AN:

250826

Hom.:

AF XY:

0.0111

AC XY:

1509

AN XY:

135538

show subpopulations

Gnomad AFR exome

AF:

0.00843

Gnomad AMR exome

AF:

0.00163

Gnomad ASJ exome

AF:

0.00449

Gnomad EAS exome

AF:

0.0666

Gnomad SAS exome

AF:

0.0178

Gnomad FIN exome

AF:

0.00190

Gnomad NFE exome

AF:

0.00576

Gnomad OTH exome

AF:

0.00639

GnomAD4 exome

AF:

0.00937

AC:

13692

AN:

1461556

Hom.:

186

Cov.:

AF XY:

0.00952

AC XY:

6920

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.00974

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.00574

Gnomad4 EAS exome

AF:

0.0728

Gnomad4 SAS exome

AF:

0.0185

Gnomad4 FIN exome

AF:

0.00155

Gnomad4 NFE exome

AF:

0.00709

Gnomad4 OTH exome

AF:

0.0107

GnomAD4 genome

AF:

0.00892

AC:

1358

AN:

152242

Hom.:

Cov.:

AF XY:

0.00993

AC XY:

739

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00912

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.0719

Gnomad4 SAS

AF:

0.0216

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00657

Gnomad4 OTH

AF:

0.00569

Alfa

AF:

0.00652

Hom.:

Bravo

AF:

0.00940

Asia WGS

AF:

0.0510

AC:

177

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 12, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00085

dbscSNV1_RF

Benign

0.050

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