3-36443331-C-T

Position:

• chr3-36443331-C-T

Variant summary

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

The NM_003149.3(STAC):​c.112-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,611,396 control chromosomes in the GnomAD database, including 33,636 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 0.19 (2718 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30918 hom.)
• Consequence: STAC NM_003149.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618

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]

STAC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAC	NM_003149.3	c.112-33C>T		intron_variant		ENST00000273183.8	NP_003140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAC	ENST00000273183.8	c.112-33C>T		intron_variant		1	NM_003149.3	ENSP00000273183.3

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28532 AN: 152028 Hom.: 2718 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.196

GnomAD3 exomes AF: 0.202 AC: 50208 AN: 248196 Hom.: 5310 AF XY: 0.197 AC XY: 26463 AN XY: 134328

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.244

Gnomad EAS exome AF: 0.169

Gnomad SAS exome AF: 0.146

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.207

Gnomad OTH exome AF: 0.193

GnomAD4 exome AF: 0.204 AC: 298028 AN: 1459252 Hom.: 30918 Cov.: 33 AF XY: 0.203 AC XY: 146985 AN XY: 725718

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.238

Gnomad4 EAS exome AF: 0.190

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.188 AC: 28536 AN: 152144 Hom.: 2718 Cov.: 32 AF XY: 0.186 AC XY: 13849 AN XY: 74374

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.193

Alfa AF: 0.198 Hom.: 4412

Bravo AF: 0.188

Asia WGS AF: 0.180 AC: 627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.9
DANN	Benign	0.72

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: rs3749279; hg19: chr3-36484823; COSMIC: COSV56212314;