22-37206746-T-C

Variant summary

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

The NM_001051.5(SSTR3):​c.1058A>G​(p.Glu353Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

SSTR3
NM_001051.5 missense

Scores

16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.32
Variant links:
Genes affected
SSTR3 (HGNC:11332): (somatostatin receptor 3) This gene encodes a member of the somatostatin receptor protein family. Somatostatins are peptide hormones that regulate diverse cellular functions such as neurotransmission, cell proliferation, and endocrine signaling as well as inhibiting the release of many hormones and other secretory proteins. Somatostatin has two active forms of 14 and 28 amino acids. The biological effects of somatostatins are mediated by a family of G-protein coupled somatostatin receptors that are expressed in a tissue-specific manner. Somatostatin receptors form homodimers and heterodimers with other members of the superfamily as well as with other G-protein coupled receptors and receptor tyrosine kinases. This protein is functionally coupled to adenylyl cyclase. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

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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=0.074248284).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SSTR3NM_001051.5 linkuse as main transcriptc.1058A>G p.Glu353Gly missense_variant 2/2 ENST00000610913.2 NP_001042.1 P32745

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SSTR3ENST00000610913.2 linkuse as main transcriptc.1058A>G p.Glu353Gly missense_variant 2/21 NM_001051.5 ENSP00000480971.1 P32745
SSTR3ENST00000617123.1 linkuse as main transcriptc.1058A>G p.Glu353Gly missense_variant 2/21 ENSP00000481325.1 P32745

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

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 GeneticsAug 26, 2024The c.1058A>G (p.E353G) alteration is located in exon 2 (coding exon 1) of the SSTR3 gene. This alteration results from a A to G substitution at nucleotide position 1058, causing the glutamic acid (E) at amino acid position 353 to be replaced by a glycine (G). 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
0.071
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
16
DANN
Benign
0.97
DEOGEN2
Benign
0.040
T;T
Eigen
Benign
-0.70
Eigen_PC
Benign
-0.66
FATHMM_MKL
Benign
0.46
N
LIST_S2
Benign
0.34
.;T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.074
T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.46
N;N
PrimateAI
Benign
0.25
T
Sift4G
Benign
0.10
T;T
Polyphen
0.0
B;B
Vest4
0.17
MutPred
0.22
Loss of stability (P = 0.2407);Loss of stability (P = 0.2407);
MVP
0.49
ClinPred
0.073
T
GERP RS
4.3
Varity_R
0.052
gMVP
0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-37602785; API