rs76823783

chr12-57245219-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

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:3
• Conservation: PhyloP100: 3.14

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]

ACMG classification

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	UniProt
STAC3	NM_145064.3	c.604-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000332782.7

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00891 AC: 1355 AN: 152124 Hom.: 22 Cov.: 32

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.: 58 AF XY: 0.0111 AC XY: 1509 AN XY: 135538

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.: 31 AF XY: 0.00952 AC XY: 6920 AN XY: 727076

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.: 22 Cov.: 32 AF XY: 0.00993 AC XY: 739 AN XY: 74434

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.: 4

Bravo AF: 0.00940

Asia WGS AF: 0.0510 AC: 177 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 12, 2021

- -

Bailey-Bloch congenital myopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	14
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

Other links and lift over

dbSNP: rs76823783; hg19: chr12-57639002; COSMIC: COSV60414248; COSMIC: COSV60414248;