4-26861325-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020860.4(STIM2):​c.107C>T​(p.Ser36Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000647 in 1,390,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

STIM2
NM_020860.4 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14
Variant links:
Genes affected
STIM2 (HGNC:19205): (stromal interaction molecule 2) This gene is a member of the stromal interaction molecule (STIM) family and likely arose, along with related family member STIM1, from a common ancestral gene. The encoded protein functions to regulate calcium concentrations in the cytosol and endoplasmic reticulum, and is involved in the activation of plasma membrane Orai Ca(2+) entry channels. This gene initiates translation from a non-AUG (UUG) start site. A signal peptide is cleaved from the resulting protein. Multiple transcript variants result from alternative splicing. [provided by RefSeq, Dec 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.133421).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
STIM2NM_020860.4 linkuse as main transcriptc.107C>T p.Ser36Phe missense_variant 1/12 ENST00000467087.7 NP_065911.3 Q9P246-1B3KUB5
STIM2NM_001169118.2 linkuse as main transcriptc.107C>T p.Ser36Phe missense_variant 1/13 NP_001162589.1 Q9P246H0Y860B3KUB5
STIM2NM_001169117.2 linkuse as main transcriptc.107C>T p.Ser36Phe missense_variant 1/13 NP_001162588.1 Q9P246-3B3KUB5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
STIM2ENST00000467087.7 linkuse as main transcriptc.107C>T p.Ser36Phe missense_variant 1/121 NM_020860.4 ENSP00000419073.2 Q9P246-1A0A1X7SBY3

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151818
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000195
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000947
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000638
AC:
2
AN:
31338
Hom.:
0
AF XY:
0.000106
AC XY:
2
AN XY:
18888
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000142
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000856
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000565
AC:
7
AN:
1239030
Hom.:
0
Cov.:
31
AF XY:
0.00000494
AC XY:
3
AN XY:
607794
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000735
Gnomad4 SAS exome
AF:
0.0000503
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000198
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
151818
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74144
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000195
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000947
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.0000624
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 29, 2024The c.107C>T (p.S36F) alteration is located in exon 1 (coding exon 1) of the STIM2 gene. This alteration results from a C to T substitution at nucleotide position 107, causing the serine (S) at amino acid position 36 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Benign
0.045
.;T;T;T;.
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.085
N
LIST_S2
Benign
0.81
T;T;T;T;T
M_CAP
Pathogenic
0.89
D
MetaRNN
Benign
0.13
T;T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.90
.;.;.;L;.
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-0.26
N;N;N;.;.
REVEL
Benign
0.082
Sift
Benign
0.084
T;T;T;.;.
Sift4G
Uncertain
0.037
D;D;D;.;.
Vest4
0.20
MVP
0.30
ClinPred
0.054
T
GERP RS
2.3
Varity_R
0.054
gMVP
0.40

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs770231794; hg19: chr4-26862947; API