chr3-52840272-T-C

Position:

• chr3-52840272-T-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BA1

The NM_198563.5(STIMATE):​c.*222A>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 0.24 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 NM_198563.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40

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]

STIMATE (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STIMATE	NM_198563.5	c.*222A>G		3_prime_UTR_variant	8/8	ENST00000355083.11	NP_940965.1
STIMATE-MUSTN1	NM_001198974.3	c.879+228A>G		intron_variant			NP_001185903.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STIMATE	ENST00000355083	c.*222A>G		3_prime_UTR_variant	8/8	1	NM_198563.5	ENSP00000347195.5
STIMATE-MUSTN1	ENST00000504329.1	c.879+228A>G		intron_variant		5		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

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.412

Gnomad4 ASJ exome AF: 0.318

Gnomad4 EAS exome AF: 0.351

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.247

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.234

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

Gnomad4 AFR AF: 0.199

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.243

Alfa AF: 0.251 Hom.: 8986

Bravo AF: 0.256

Asia WGS AF: 0.237 AC: 821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.11
CADD	Benign	17
DANN	Benign	0.90

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: rs6445538; hg19: chr3-52874288;