rs6445538

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-52840272-T-A
• chr3-52840272-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000477591.1(STIMATE):​n.434A>T 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 0.00000293 in 341,242 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>T		3_prime_UTR	Exon 8 of 8	NP_940965.1
	STIMATE-MUSTN1	NM_001198974.3		c.879+228A>T		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>T		non_coding_transcript_exon	Exon 2 of 2
	STIMATE	ENST00000355083.11	TSL:1 MANE Select	c.*222A>T		3_prime_UTR	Exon 8 of 8	ENSP00000347195.5
	STIMATE-MUSTN1	ENST00000504329.1	TSL:5	c.879+228A>T		intron	N/A	ENSP00000422941.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000293 AC: 1 AN: 341242 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 178332

African (AFR) AF: 0.00 AC: 0 AN: 10002

American (AMR) AF: 0.00 AC: 0 AN: 13156

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10980

East Asian (EAS) AF: 0.00 AC: 0 AN: 23982

South Asian (SAS) AF: 0.00 AC: 0 AN: 31920

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22024

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1568

European-Non Finnish (NFE) AF: 0.00000482 AC: 1 AN: 207450

Other (OTH) AF: 0.00 AC: 0 AN: 20160

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Uncertain	0.010
CADD	Benign	17
DANN	Benign	0.93
PhyloP100		2.4
PromoterAI		0.0069	Neutral

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;