Genetic Variant STAC:p.Pro7Ser (chr3-36380662-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003149.3(STAC):c.19C>T(p.Pro7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000325 in 1,599,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

STAC
NM_003149.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.944

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:

LOC124906227 (HGNC:):

LOC124906227 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024422705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STAC	NM_003149.3 link	c.19C>T	p.Pro7Ser	missense_variant	Exon 1 of 11	ENST00000273183.8	NP_003140.1	Q99469Q8WUK8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAC	ENST00000273183.8 link	c.19C>T	p.Pro7Ser	missense_variant	Exon 1 of 11	1	NM_003149.3	ENSP00000273183.3		Q99469

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000361

AC:

AN:

221408

Hom.:

AF XY:

0.0000416

AC XY:

AN XY:

120282

show subpopulations

Gnomad AFR exome

AF:

0.000635

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000187

AC:

AN:

1447128

Hom.:

Cov.:

AF XY:

0.0000209

AC XY:

AN XY:

718260

show subpopulations

Gnomad4 AFR exome

AF:

0.000693

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.0000334

GnomAD4 genome

AF:

0.000164

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.000603

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000978

Hom.:

Bravo

AF:

0.000234

ExAC

AF:

0.0000580

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 16, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.19C>T (p.P7S) alteration is located in exon 1 (coding exon 1) of the STAC gene. This alteration results from a C to T substitution at nucleotide position 19, causing the proline (P) at amino acid position 7 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0026

T;T;T

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.84

T;T;T

M_CAP

Benign

0.068

MetaRNN

Benign

0.024

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.

PrimateAI

Benign

0.47

PROVEAN

Benign

0.47

N;N;N

REVEL

Benign

0.047

Sift

Benign

0.45

T;T;T

Sift4G

Benign

0.18

T;T;T

Polyphen

0.0010

B;B;.

Vest4

0.069

MVP

0.60

MPC

0.18

ClinPred

0.018

GERP RS

0.47

Varity_R

0.026

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over