Genetic Variant STAC:c.112-33C>T (chr3-36443331-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.618

Publications

13 publications found

Variant links:

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 links:

ENSG00000303138 (HGNC:):

ENSG00000303138 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAC	NM_003149.3 link	c.112-33C>T		intron_variant	Intron 1 of 10	ENST00000273183.8	NP_003140.1	Q99469Q8WUK8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAC	ENST00000273183.8 link	c.112-33C>T		intron_variant	Intron 1 of 10	1	NM_003149.3	ENSP00000273183.3		Q99469

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28532

AN:

152028

Hom.:

2718

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.203

AC XY:

146985

AN XY:

725718

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

13109

26218

39328

52437

65546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8060

16120

24180

32240

40300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.188

AC:

28536

AN:

152144

Hom.:

2718

Cov.:

AF XY:

0.186

AC XY:

13849

AN XY:

74374

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.210

AC:

14279

AN:

67974

Other (OTH)

AF:

0.193

AC:

407

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1178

2355

3533

4710

5888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

300

600

900

1200

1500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.9

(source)

DANN

Benign

0.72

PhyloP100

0.62

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over