rs11711733

chr3-36505641-A-Gchr3-36505641-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003149.3(STAC):c.832-105A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 735,552 control chromosomes in the GnomAD database, including 7,925 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1894 hom., cov: 32)
  • Exomes 𝑓: 0.14 (6031 hom.)
• Consequence: STAC NM_003149.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320

Genes affected

STAC (HGNC:11353): (SH3 and cysteine rich domain) Predicted to enable transmembrane transporter binding activity. Predicted to be involved in positive regulation of protein localization to plasma membrane; positive regulation of voltage-gated calcium channel activity; and skeletal muscle contraction. Predicted to act upstream of or within cellular response to heat; muscle contraction; and regulation of voltage-gated calcium channel activity. Predicted to be located in T-tubule. Predicted to be extrinsic component of cytoplasmic side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAC	NM_003149.3	c.832-105A>G		intron_variant		ENST00000273183.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAC	ENST00000273183.8	c.832-105A>G		intron_variant		1	NM_003149.3	P1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22885 AN: 152054 Hom.: 1895 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0706

Gnomad FIN AF: 0.0744

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.136 AC: 79061 AN: 583380 Hom.: 6031 AF XY: 0.133 AC XY: 41426 AN XY: 312564

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.0870

Gnomad4 ASJ exome AF: 0.172

Gnomad4 EAS exome AF: 0.000844

Gnomad4 SAS exome AF: 0.0771

Gnomad4 FIN exome AF: 0.0862

Gnomad4 NFE exome AF: 0.159

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome AF: 0.151 AC: 22915 AN: 152172 Hom.: 1894 Cov.: 32 AF XY: 0.144 AC XY: 10745 AN XY: 74406

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0711

Gnomad4 FIN AF: 0.0744

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.154

Alfa AF: 0.148 Hom.: 992

Bravo AF: 0.155

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.24
Dann	Benign	0.67

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

Other links and lift over

dbSNP: rs11711733; hg19: chr3-36547133;