Variant chr12-57243934-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_145064.3(STAC3):c.997-24A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,611,978 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.0025 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 78 hom. )

Consequence

STAC3
NM_145064.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.612

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 -14 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 2 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-57243934-T-C is Benign according to our data. Variant chr12-57243934-T-C is described in ClinVar as [Benign]. Clinvar id is 1222559.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0557 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.997-24A>G		intron_variant		ENST00000332782.7	NP_659501.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
STAC3	ENST00000332782.7 linkuse as main transcript	c.997-24A>G	intron_variant	2	NM_145064.3	ENSP00000329200	P1	Q96MF2-1
STAC3	ENST00000554578.5 linkuse as main transcript	c.880-24A>G	intron_variant	1		ENSP00000452068		Q96MF2-2
STAC3	ENST00000557176.5 linkuse as main transcript	c.*57-24A>G	intron_variant, NMD_transcript_variant	1		ENSP00000450740
STAC3	ENST00000546246.2 linkuse as main transcript	c.439-24A>G	intron_variant	2		ENSP00000441515		Q96MF2-3

Frequencies

GnomAD3 genomes

AF:

0.00254

AC:

386

AN:

151956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00866

Gnomad EAS

AF:

0.0613

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00384

GnomAD3 exomes

AF:

0.00551

AC:

1357

AN:

246452

Hom.:

AF XY:

0.00512

AC XY:

684

AN XY:

133570

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000234

Gnomad ASJ exome

AF:

0.0102

Gnomad EAS exome

AF:

0.0648

Gnomad SAS exome

AF:

0.000959

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000279

Gnomad OTH exome

AF:

0.00316

GnomAD4 exome

AF:

0.00219

AC:

3201

AN:

1459904

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

1574

AN XY:

726224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000270

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.0646

Gnomad4 SAS exome

AF:

0.00101

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000765

Gnomad4 OTH exome

AF:

0.00302

GnomAD4 genome

AF:

0.00253

AC:

385

AN:

152074

Hom.:

Cov.:

AF XY:

0.00269

AC XY:

200

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00866

Gnomad4 EAS

AF:

0.0613

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00380

Alfa

AF:

0.00253

Hom.:

Bravo

AF:

0.00317

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.7

DANN

Benign

0.73

La Branchor

0.65

BranchPoint Hunter

2.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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