3-36380681-A-C

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.38A>C(p.Asp13Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00323 in 1,608,662 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (60 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (68 hom.)
• Consequence: STAC NM_003149.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.88

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]

LOC124906227 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002518326).
• BP6: Variant 3-36380681-A-C is Benign according to our data. Variant chr3-36380681-A-C is described in ClinVar as [Benign]. Clinvar id is 767893.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAC	NM_003149.3	c.38A>C	p.Asp13Ala	missense_variant	1/11	ENST00000273183.8
LOC124906227	XR_007095868.1	n.148-44976T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAC	ENST00000273183.8	c.38A>C	p.Asp13Ala	missense_variant	1/11	1	NM_003149.3	P1

Frequencies

GnomAD3 genomes AF: 0.0170 AC: 2592 AN: 152144 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.0585

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00818

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00448 AC: 1063 AN: 237206 Hom.: 28 AF XY: 0.00325 AC XY: 421 AN XY: 129372

Gnomad AFR exome AF: 0.0629

Gnomad AMR exome AF: 0.00394

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000344

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000207

Gnomad OTH exome AF: 0.00345

GnomAD4 exome AF: 0.00179 AC: 2609 AN: 1456400 Hom.: 68 Cov.: 32 AF XY: 0.00157 AC XY: 1140 AN XY: 723964

Gnomad4 AFR exome AF: 0.0602

Gnomad4 AMR exome AF: 0.00443

Gnomad4 ASJ exome AF: 0.0000386

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000165

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000122

Gnomad4 OTH exome AF: 0.00389

GnomAD4 genome AF: 0.0170 AC: 2594 AN: 152262 Hom.: 60 Cov.: 32 AF XY: 0.0163 AC XY: 1217 AN XY: 74464

Gnomad4 AFR AF: 0.0584

Gnomad4 AMR AF: 0.00817

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.000764 Hom.: 0

Bravo AF: 0.0203

ESP6500AA AF: 0.0531 AC: 233

ESP6500EA AF: 0.000351 AC: 3

ExAC AF: 0.00531 AC: 643

Asia WGS AF: 0.00173 AC: 6 AN: 3478

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

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.26
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0095	T;T;T
Eigen	Benign	0.087
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.72	T;T;T
MetaRNN	Benign	0.0025	T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.4	L;.;.
MutationTaster	Benign	0.71	N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.047
Sift	Benign	0.15	T;T;D
Sift4G	Benign	0.43	T;T;T
Polyphen		0.52	P;P;.
Vest4		0.36
MVP		0.72
MPC		0.36
ClinPred		0.020	T
GERP RS		5.0
Varity_R		0.21
gMVP		0.31

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

Other links and lift over

dbSNP: rs149680537; hg19: chr3-36422173; COSMIC: COSV99830629; COSMIC: COSV99830629;