3-52837913-G-C

Variant names:

• chr3-52837913-G-C
• rs3733047
• NM_198563.5:c.*2581C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198563.5(STIMATE):​c.*2581C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,018 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 33)
• Consequence: STIMATE NM_198563.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STIMATE	NM_198563.5	c.*2581C>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000355083.11	NP_940965.1
STIMATE-MUSTN1	NM_001198974.3	c.879+2587C>G		intron_variant	Intron 8 of 9		NP_001185903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STIMATE	ENST00000355083	c.*2581C>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_198563.5	ENSP00000347195.5
STIMATE-MUSTN1	ENST00000504329.1	c.879+2587C>G		intron_variant	Intron 8 of 9	5		ENSP00000422941.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152018 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152018 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74234

Gnomad4 AFR AF: 0.0000725

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.4
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3733047; hg19: chr3-52871929;