3-52879263-C-T

Variant names:

• chr3-52879263-C-T
• rs3796352
• NM_198563.5:c.160+18028G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198563.5(STIMATE):​c.160+18028G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0664 in 152,268 control chromosomes in the GnomAD database, including 421 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 0.066 (421 hom., cov: 32)
• Consequence: STIMATE NM_198563.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• Publications: 17 publications found

Genes affected

STIMATE (HGNC:30526): (STIM activating enhancer) Enables calcium channel regulator activity. Involved in activation of store-operated calcium channel activity; calcium-mediated signaling using intracellular calcium source; and positive regulation of calcineurin-NFAT signaling cascade. Located in cortical endoplasmic reticulum; endoplasmic reticulum membrane; and endoplasmic reticulum-plasma membrane contact site. [provided by Alliance of Genome Resources, Apr 2022]

STIMATE-MUSTN1 (HGNC:38834): (STIMATE-MUSTN1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring TMEM110 (transmembrane protein 110) and MUSTN1 (musculoskeletal, embryonic nuclear protein 1) genes. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0919 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198563.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIMATE	NM_198563.5	MANE Select	c.160+18028G>A		intron	N/A	NP_940965.1	Q86TL2
	STIMATE-MUSTN1	NM_001198974.3		c.160+18028G>A		intron	N/A	NP_001185903.2	A8MSY1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIMATE	ENST00000355083.11	TSL:1 MANE Select	c.160+18028G>A		intron	N/A	ENSP00000347195.5	Q86TL2
	STIMATE-MUSTN1	ENST00000504329.1	TSL:5	c.160+18028G>A		intron	N/A	ENSP00000422941.1	A8MSY1
	STIMATE	ENST00000963054.1		c.160+18028G>A		intron	N/A	ENSP00000633113.1

Frequencies

GnomAD3 genomes AF: 0.0665 AC: 10112 AN: 152150 Hom.: 421 Cov.: 32

Gnomad AFR AF: 0.0181

Gnomad AMI AF: 0.0870

Gnomad AMR AF: 0.0918

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0386

Gnomad SAS AF: 0.0392

Gnomad FIN AF: 0.0516

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0939

Gnomad OTH AF: 0.0832

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

GnomAD4 genome AF: 0.0664 AC: 10109 AN: 152268 Hom.: 421 Cov.: 32 AF XY: 0.0633 AC XY: 4715 AN XY: 74458

African (AFR) AF: 0.0180 AC: 750 AN: 41562

American (AMR) AF: 0.0916 AC: 1401 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 358 AN: 3468

East Asian (EAS) AF: 0.0387 AC: 201 AN: 5190

South Asian (SAS) AF: 0.0394 AC: 190 AN: 4822

European-Finnish (FIN) AF: 0.0516 AC: 547 AN: 10604

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0939 AC: 6383 AN: 68012

Other (OTH) AF: 0.0828 AC: 175 AN: 2114

Alfa AF: 0.0875 Hom.: 1998

Bravo AF: 0.0680

Asia WGS AF: 0.0470 AC: 165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.5
DANN	Benign	0.45
PhyloP100		0.034
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3796352; hg19: chr3-52913279;