3-36504411-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003149.3(STAC):c.785A>G(p.Asn262Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00475 in 1,613,536 control chromosomes in the GnomAD database, including 254 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.024 (129 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (125 hom.)
• Consequence: STAC NM_003149.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.66

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021566153).
• BP6: Variant 3-36504411-A-G is Benign according to our data. Variant chr3-36504411-A-G is described in ClinVar as [Benign]. Clinvar id is 783216.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAC	NM_003149.3	c.785A>G	p.Asn262Ser	missense_variant	7/11	ENST00000273183.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAC	ENST00000273183.8	c.785A>G	p.Asn262Ser	missense_variant	7/11	1	NM_003149.3	P1

Frequencies

GnomAD3 genomes AF: 0.0238 AC: 3620 AN: 152166 Hom.: 128 Cov.: 32

Gnomad AFR AF: 0.0804

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00827

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0163

GnomAD3 exomes AF: 0.00700 AC: 1757 AN: 250826 Hom.: 60 AF XY: 0.00523 AC XY: 709 AN XY: 135544

Gnomad AFR exome AF: 0.0823

Gnomad AMR exome AF: 0.00473

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0105

Gnomad SAS exome AF: 0.000457

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.00295

GnomAD4 exome AF: 0.00276 AC: 4030 AN: 1461252 Hom.: 125 Cov.: 30 AF XY: 0.00247 AC XY: 1797 AN XY: 726930

Gnomad4 AFR exome AF: 0.0831

Gnomad4 AMR exome AF: 0.00549

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00716

Gnomad4 SAS exome AF: 0.000429

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000321

Gnomad4 OTH exome AF: 0.00499

GnomAD4 genome AF: 0.0238 AC: 3630 AN: 152284 Hom.: 129 Cov.: 32 AF XY: 0.0232 AC XY: 1725 AN XY: 74464

Gnomad4 AFR AF: 0.0804

Gnomad4 AMR AF: 0.0117

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00810

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.00567 Hom.: 45

Bravo AF: 0.0271

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0733 AC: 323

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00828 AC: 1005

Asia WGS AF: 0.00953 AC: 33 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.34
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.0099	T;T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D;D;D
MetaRNN	Benign	0.0022	T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.4	M;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.35	T;T;T
Sift4G	Benign	0.19	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.48
MVP		0.77
MPC		0.64
ClinPred		0.032	T
GERP RS		5.4
Varity_R		0.15
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs7634545; hg19: chr3-36545903; COSMIC: COSV99830630;