3-36443331-C-T

Variant names:

• chr3-36443331-C-T
• rs3749279
• NM_003149.3:c.112-33C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

ENSG00000303138 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003149.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAC	NM_003149.3	MANE Select	c.112-33C>T		intron	N/A	NP_003140.1	Q99469
	STAC	NM_001292049.2		c.112-33C>T		intron	N/A	NP_001278978.1	E9PEA7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAC	ENST00000273183.8	TSL:1 MANE Select	c.112-33C>T		intron	N/A	ENSP00000273183.3	Q99469
	STAC	ENST00000476388.5	TSL:1	n.307-33C>T		intron	N/A
	STAC	ENST00000903142.1		c.112-66C>T		intron	N/A	ENSP00000573201.1

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

GnomAD2 exomes AF: 0.202 AC: 50208 AN: 248196 AF XY: 0.197

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 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

African (AFR) AF: 0.127 AC: 4232 AN: 33412

American (AMR) AF: 0.275 AC: 12280 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 6212 AN: 26052

East Asian (EAS) AF: 0.190 AC: 7540 AN: 39690

South Asian (SAS) AF: 0.142 AC: 12180 AN: 85744

European-Finnish (FIN) AF: 0.202 AC: 10757 AN: 53284

Middle Eastern (MID) AF: 0.171 AC: 928 AN: 5412

European-Non Finnish (NFE) AF: 0.209 AC: 231863 AN: 1110774

Other (OTH) AF: 0.200 AC: 12036 AN: 60292

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

African (AFR) AF: 0.134 AC: 5573 AN: 41534

American (AMR) AF: 0.228 AC: 3487 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 826 AN: 3472

East Asian (EAS) AF: 0.173 AC: 894 AN: 5156

South Asian (SAS) AF: 0.144 AC: 694 AN: 4810

European-Finnish (FIN) AF: 0.202 AC: 2141 AN: 10586

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14279 AN: 67974

Other (OTH) AF: 0.193 AC: 407 AN: 2114

Alfa AF: 0.198 Hom.: 5495

Bravo AF: 0.188

Asia WGS AF: 0.180 AC: 627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.9
DANN	Benign	0.72
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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