22-37207289-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001051.5(SSTR3):c.515C>T(p.Ala172Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000347 in 1,440,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SSTR3 NM_001051.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.32

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]

ACMG classification

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=0.12129673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SSTR3	NM_001051.5	c.515C>T	p.Ala172Val	missense_variant	2/2	ENST00000610913.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SSTR3	ENST00000610913.2	c.515C>T	p.Ala172Val	missense_variant	2/2	1	NM_001051.5	P1
SSTR3	ENST00000617123.1	c.515C>T	p.Ala172Val	missense_variant	2/2	1		P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.0000261 AC: 6 AN: 229742 Hom.: 0 AF XY: 0.0000161 AC XY: 2 AN XY: 124542

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000336

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000347 AC: 5 AN: 1440530 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 714154

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000127

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Bravo AF: 0.0000113

ExAC AF: 0.0000334 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 16, 2023

The c.515C>T (p.A172V) alteration is located in exon 2 (coding exon 1) of the SSTR3 gene. This alteration results from a C to T substitution at nucleotide position 515, causing the alanine (A) at amino acid position 172 to be replaced by a valine (V). 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	0.091
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.33
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.029	T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.056
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.15	N;N
MutationTaster	Benign	0.95	D;D
PrimateAI	Uncertain	0.63	T
Sift4G	Benign	0.12	T;T
Polyphen		0.11	B;B
Vest4		0.30
MutPred		0.49		Loss of glycosylation at S171 (P = 0.0621);Loss of glycosylation at S171 (P = 0.0621);
MVP		0.32
ClinPred		0.48	T
GERP RS		5.6
Varity_R		0.12
gMVP		0.43

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: rs759921363; hg19: chr22-37603328;