dbSNP rs202179964: SSTR5:p.Ser35Trp (chr16-1078972-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001172560.3(SSTR5):c.104C>G(p.Ser35Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SSTR5
NM_001172560.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.26

Variant links:

Genes affected

SSTR5 (HGNC:11334): (somatostatin receptor 5) Somatostatin and its related peptide cortistatin exert multiple biological actions on normal and tumoral tissue targets by interacting with somatostatin receptors (SSTRs). The protein encoded by this gene is one of the SSTRs, which is a multi-pass membrane protein and belongs to the G-protein coupled receptor 1 family. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase, and different regions of this receptor molecule are required for the activation of different signaling pathways. A mutation in this gene results in somatostatin analog resistance. Alternatively spliced transcript variants have been identified in this gene.[provided by RefSeq, Feb 2010]

SSTR5 links:

SSTR5-AS1 (HGNC:26502): (SSTR5 antisense RNA 1)

SSTR5-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3382734).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSTR5	NM_001172560.3 link	c.104C>G	p.Ser35Trp	missense_variant	Exon 2 of 2	ENST00000689027.1	NP_001166031.1	P35346
SSTR5	NM_001053.4 link	c.104C>G	p.Ser35Trp	missense_variant	Exon 1 of 1		NP_001044.1	P35346
SSTR5-AS1	NR_027242.1 link	n.-241G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SSTR5	ENST00000689027.1 link	c.104C>G	p.Ser35Trp	missense_variant	Exon 2 of 2		NM_001172560.3	ENSP00000508487.1	P35346
SSTR5	ENST00000293897.6 link	c.104C>G	p.Ser35Trp	missense_variant	Exon 1 of 1	6		ENSP00000293897.4	P35346
SSTR5-AS1	ENST00000624643.1 link	n.-241G>C		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.95e-7

AC:

AN:

1439374

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

714798

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.07e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.79

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.34

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.3

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.5

REVEL

Benign

0.24

Sift

Uncertain

0.0080

Sift4G

Benign

0.088

Polyphen

0.99

Vest4

0.23

MutPred

0.49

Loss of disorder (P = 0.0017);

MVP

0.80

MPC

0.70

ClinPred

0.39

GERP RS

2.1

Varity_R

0.058

gMVP

0.41

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over