22-37206911-A-C

Position:

• chr22-37206911-A-C

Variant summary

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

The NM_001051.5(SSTR3):​c.893T>G​(p.Val298Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSTR3	NM_001051.5	c.893T>G	p.Val298Gly	missense_variant	2/2	ENST00000610913.2	NP_001042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSTR3	ENST00000610913.2	c.893T>G	p.Val298Gly	missense_variant	2/2	1	NM_001051.5	ENSP00000480971.1
SSTR3	ENST00000617123.1	c.893T>G	p.Val298Gly	missense_variant	2/2	1		ENSP00000481325.1

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2024

The c.893T>G (p.V298G) alteration is located in exon 2 (coding exon 1) of the SSTR3 gene. This alteration results from a T to G substitution at nucleotide position 893, causing the valine (V) at amino acid position 298 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	Uncertain	0.49
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;T
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	.;D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Uncertain	0.63	T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.95	P;P
Vest4		0.70
MutPred		0.56		Loss of stability (P = 0.0086);Loss of stability (P = 0.0086);
MVP		0.76
ClinPred		0.89	D
GERP RS		3.2
Varity_R		0.37
gMVP		0.70

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: chr22-37602950;