Genetic Variant NM_003149.3:c.832-105A>G (chr3-36505641-A-G) – 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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.320

Publications

6 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:

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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=-0.83).

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 rank	MANE	Protein	UniProt
STAC	NM_003149.3 link	c.832-105A>G		intron_variant	Intron 7 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.832-105A>G		intron_variant	Intron 7 of 10	1	NM_003149.3	ENSP00000273183.3		Q99469

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22885

AN:

152054

Hom.:

1895

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.199

AC:

2714

AN:

13610

American (AMR)

AF:

0.0870

AC:

1543

AN:

17734

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

3094

AN:

18036

East Asian (EAS)

AF:

0.000844

AC:

AN:

30808

South Asian (SAS)

AF:

0.0771

AC:

4039

AN:

52360

European-Finnish (FIN)

AF:

0.0862

AC:

4086

AN:

47398

Middle Eastern (MID)

AF:

0.0886

AC:

211

AN:

2382

European-Non Finnish (NFE)

AF:

0.159

AC:

58994

AN:

370878

Other (OTH)

AF:

0.144

AC:

4354

AN:

30174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

3211

6421

9632

12842

16053

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

804

1608

2412

3216

4020

<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:

0.151

AC:

22915

AN:

152172

Hom.:

1894

Cov.:

AF XY:

0.144

AC XY:

10745

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.200

AC:

8307

AN:

41510

American (AMR)

AF:

0.106

AC:

1619

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

614

AN:

3468

East Asian (EAS)

AF:

0.00309

AC:

AN:

5178

South Asian (SAS)

AF:

0.0711

AC:

343

AN:

4826

European-Finnish (FIN)

AF:

0.0744

AC:

790

AN:

10612

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.157

AC:

10666

AN:

67976

Other (OTH)

AF:

0.154

AC:

325

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

968

1937

2905

3874

4842

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

236

472

708

944

1180

<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:

0.147

Hom.:

1343

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

(source)

DANN

Benign

0.67

PhyloP100

-0.32

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