Genetic Variant SSTR5:p.Gly23Gly (chr16-1078937-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001172560.3(SSTR5):c.69C>T(p.Gly23Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,600,332 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

SSTR5
NM_001172560.3 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.948

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 16-1078937-C-T is Benign according to our data. Variant chr16-1078937-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3052332.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.948 with no splicing effect.

BS2

High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSTR5	NM_001172560.3 link	c.69C>T	p.Gly23Gly	synonymous_variant	Exon 2 of 2	ENST00000689027.1	NP_001166031.1	P35346
SSTR5	NM_001053.4 link	c.69C>T	p.Gly23Gly	synonymous_variant	Exon 1 of 1		NP_001044.1	P35346
SSTR5-AS1	NR_027242.1 link	n.-206G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SSTR5	ENST00000689027.1 link	c.69C>T	p.Gly23Gly	synonymous_variant	Exon 2 of 2		NM_001172560.3	ENSP00000508487.1	P35346
SSTR5	ENST00000293897.6 link	c.69C>T	p.Gly23Gly	synonymous_variant	Exon 1 of 1	6		ENSP00000293897.4	P35346
SSTR5-AS1	ENST00000566499.1 link	n.-230G>A		upstream_gene_variant		4
SSTR5-AS1	ENST00000624643.1 link	n.-206G>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000502

AC:

AN:

219188

Hom.:

AF XY:

0.0000249

AC XY:

AN XY:

120564

show subpopulations

Gnomad AFR exome

AF:

0.000627

Gnomad AMR exome

AF:

0.0000307

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000207

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000152

AC:

AN:

1448016

Hom.:

Cov.:

AF XY:

0.00000834

AC XY:

AN XY:

719830

show subpopulations

Gnomad4 AFR exome

AF:

0.000392

Gnomad4 AMR exome

AF:

0.0000230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000542

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000566

Hom.:

Bravo

AF:

0.000110

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SSTR5-related disorder

Benign:1

Aug 20, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.9

DANN

Benign

0.78

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over