rs6769789

Positions:

• chr3-52840430-C-T

Variant summary

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

The NM_198563.5(STIMATE):​c.*64G>A variant causes a 3 prime UTR 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 NM_198563.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STIMATE	NM_198563.5	c.*64G>A		3_prime_UTR_variant	8/8	ENST00000355083.11	NP_940965.1
STIMATE-MUSTN1	NM_001198974.3	c.879+70G>A		intron_variant			NP_001185903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STIMATE	ENST00000355083.11	c.*64G>A		3_prime_UTR_variant	8/8	1	NM_198563.5	ENSP00000347195	P1
STIMATE	ENST00000477591.1	n.276G>A		non_coding_transcript_exon_variant	2/2	1
STIMATE	ENST00000482155.1	c.108+70G>A		intron_variant		4		ENSP00000418967
STIMATE	ENST00000464769.1	n.406G>A		non_coding_transcript_exon_variant	3/3	4

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

Gnomad4 AFR exome AF: 0.259

Gnomad4 AMR exome AF: 0.416

Gnomad4 ASJ exome AF: 0.563

Gnomad4 EAS exome AF: 0.594

Gnomad4 SAS exome AF: 0.610

Gnomad4 FIN exome AF: 0.637

Gnomad4 NFE exome AF: 0.616

Gnomad4 OTH exome AF: 0.592

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

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.528

Alfa AF: 0.573 Hom.: 24845

Bravo AF: 0.474

Asia WGS AF: 0.547 AC: 1905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.74
DANN	Benign	0.84

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: rs6769789; hg19: chr3-52874446; COSMIC: COSV61890638; COSMIC: COSV61890638;