rs6769789

Variant names:

• chr3-52840430-C-T
• rs6769789
• ENST00000477591.1:n.276G>A

Variant summary

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

The ENST00000477591.1(STIMATE):​n.276G>A 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 0.59 in 1,551,786 control chromosomes in the GnomAD database, including 275,722 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 0.50 (20857 hom., cov: 33)
  • Exomes 𝑓: 0.60 (254865 hom.)
• Consequence: STIMATE ENST00000477591.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 25 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 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.*64G>A		3_prime_UTR	Exon 8 of 8	NP_940965.1
	STIMATE-MUSTN1	NM_001198974.3		c.879+70G>A		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.276G>A		non_coding_transcript_exon	Exon 2 of 2
	STIMATE	ENST00000355083.11	TSL:1 MANE Select	c.*64G>A		3_prime_UTR	Exon 8 of 8	ENSP00000347195.5
	STIMATE-MUSTN1	ENST00000504329.1	TSL:5	c.879+70G>A		intron	N/A	ENSP00000422941.1

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76171 AN: 151988 Hom.: 20856 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.530

GnomAD4 exome AF: 0.599 AC: 838712 AN: 1399680 Hom.: 254865 Cov.: 20 AF XY: 0.601 AC XY: 417668 AN XY: 695136

African (AFR) AF: 0.259 AC: 8327 AN: 32098

American (AMR) AF: 0.416 AC: 17803 AN: 42810

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 13678 AN: 24288

East Asian (EAS) AF: 0.594 AC: 23031 AN: 38800

South Asian (SAS) AF: 0.610 AC: 49793 AN: 81656

European-Finnish (FIN) AF: 0.637 AC: 32675 AN: 51276

Middle Eastern (MID) AF: 0.609 AC: 3125 AN: 5130

European-Non Finnish (NFE) AF: 0.616 AC: 655984 AN: 1065684

Other (OTH) AF: 0.592 AC: 34296 AN: 57938

GnomAD4 genome AF: 0.501 AC: 76189 AN: 152106 Hom.: 20857 Cov.: 33 AF XY: 0.504 AC XY: 37447 AN XY: 74348

African (AFR) AF: 0.271 AC: 11250 AN: 41508

American (AMR) AF: 0.448 AC: 6858 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1933 AN: 3466

East Asian (EAS) AF: 0.618 AC: 3179 AN: 5142

South Asian (SAS) AF: 0.602 AC: 2903 AN: 4820

European-Finnish (FIN) AF: 0.645 AC: 6821 AN: 10574

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.611 AC: 41527 AN: 67984

Other (OTH) AF: 0.528 AC: 1116 AN: 2112

Alfa AF: 0.560 Hom.: 31273

Bravo AF: 0.474

Asia WGS AF: 0.547 AC: 1905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.74
DANN	Benign	0.84
PhyloP100		-2.4
PromoterAI		-0.018	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: rs6769789; hg19: chr3-52874446; COSMIC: COSV61890638; COSMIC: COSV61890638;