3-36515233-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003149.3(STAC):c.920+9399T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 151,828 control chromosomes in the GnomAD database, including 39,684 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 0.72 (39684 hom., cov: 29)
• Consequence: STAC NM_003149.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAC	NM_003149.3	c.920+9399T>C		intron_variant		ENST00000273183.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAC	ENST00000273183.8	c.920+9399T>C		intron_variant		1	NM_003149.3	P1
STAC	ENST00000434649.1	c.704+9399T>C		intron_variant		5
STAC	ENST00000457375.6	c.737+9399T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109271 AN: 151710 Hom.: 39644 Cov.: 29

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.619

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.719

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.720 AC: 109367 AN: 151828 Hom.: 39684 Cov.: 29 AF XY: 0.720 AC XY: 53433 AN XY: 74176

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.777

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.763

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.720

Alfa AF: 0.694 Hom.: 49318

Bravo AF: 0.734

Asia WGS AF: 0.719 AC: 2499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.4
Dann	Benign	0.49

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: rs6797696; hg19: chr3-36556725;