3-52840272-T-C

Variant names:

• chr3-52840272-T-C
• rs6445538
• ENST00000477591.1:n.434A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The ENST00000477591.1(STIMATE):​n.434A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 492,214 control chromosomes in the GnomAD database, including 15,644 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 0.25 (4865 hom., cov: 33)
  • Exomes 𝑓: 0.24 (10779 hom.)
• Consequence: STIMATE ENST00000477591.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40
• Publications: 31 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.11).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000477591.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIMATE	NM_198563.5	MANE Select	c.*222A>G		3_prime_UTR	Exon 8 of 8	NP_940965.1
	STIMATE-MUSTN1	NM_001198974.3		c.879+228A>G		intron	N/A	NP_001185903.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIMATE	ENST00000477591.1	TSL:1	n.434A>G		non_coding_transcript_exon	Exon 2 of 2
	STIMATE	ENST00000355083.11	TSL:1 MANE Select	c.*222A>G		3_prime_UTR	Exon 8 of 8	ENSP00000347195.5
	STIMATE-MUSTN1	ENST00000504329.1	TSL:5	c.879+228A>G		intron	N/A	ENSP00000422941.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37379 AN: 151942 Hom.: 4866 Cov.: 33

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.238 AC: 80918 AN: 340154 Hom.: 10779 Cov.: 4 AF XY: 0.231 AC XY: 41012 AN XY: 177770

African (AFR) AF: 0.200 AC: 1995 AN: 9980

American (AMR) AF: 0.412 AC: 5401 AN: 13100

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 3475 AN: 10944

East Asian (EAS) AF: 0.351 AC: 8369 AN: 23874

South Asian (SAS) AF: 0.115 AC: 3659 AN: 31866

European-Finnish (FIN) AF: 0.247 AC: 5421 AN: 21948

Middle Eastern (MID) AF: 0.225 AC: 351 AN: 1562

European-Non Finnish (NFE) AF: 0.230 AC: 47536 AN: 206776

Other (OTH) AF: 0.234 AC: 4711 AN: 20104

GnomAD4 genome AF: 0.246 AC: 37394 AN: 152060 Hom.: 4865 Cov.: 33 AF XY: 0.248 AC XY: 18432 AN XY: 74324

African (AFR) AF: 0.199 AC: 8246 AN: 41508

American (AMR) AF: 0.377 AC: 5758 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1091 AN: 3464

East Asian (EAS) AF: 0.320 AC: 1651 AN: 5158

South Asian (SAS) AF: 0.129 AC: 622 AN: 4830

European-Finnish (FIN) AF: 0.260 AC: 2747 AN: 10562

Middle Eastern (MID) AF: 0.236 AC: 69 AN: 292

European-Non Finnish (NFE) AF: 0.240 AC: 16333 AN: 67956

Other (OTH) AF: 0.243 AC: 512 AN: 2104

Alfa AF: 0.248 Hom.: 13187

Bravo AF: 0.256

Asia WGS AF: 0.237 AC: 821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.11
CADD	Benign	17
DANN	Benign	0.90
PhyloP100		2.4
PromoterAI		0.020	Neutral
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: rs6445538; hg19: chr3-52874288;