Variant 16-1078908-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001172560.3(SSTR5):c.40G>A(p.Ala14Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,605,514 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

SSTR5
NM_001172560.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.18

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:

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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 (MetaRNN=0.0065477192).

BP6

Variant 16-1078908-G-A is Benign according to our data. Variant chr16-1078908-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2353937.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 113 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSTR5	NM_001172560.3 link	c.40G>A	p.Ala14Thr	missense_variant	2/2	ENST00000689027.1	NP_001166031.1	P35346
SSTR5	NM_001053.4 link	c.40G>A	p.Ala14Thr	missense_variant	1/1		NP_001044.1	P35346

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSTR5	ENST00000689027.1 link	c.40G>A	p.Ala14Thr	missense_variant	2/2		NM_001172560.3	ENSP00000508487.1		P35346
SSTR5	ENST00000293897.6 link	c.40G>A	p.Ala14Thr	missense_variant	1/1	6		ENSP00000293897.4		P35346

Frequencies

GnomAD3 genomes

AF:

0.000743

AC:

113

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00113

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000688

AC:

159

AN:

231232

Hom.:

AF XY:

0.000730

AC XY:

AN XY:

127462

show subpopulations

Gnomad AFR exome

AF:

0.000508

Gnomad AMR exome

AF:

0.000590

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00147

Gnomad SAS exome

AF:

0.0000670

Gnomad FIN exome

AF:

0.0000579

Gnomad NFE exome

AF:

0.000947

Gnomad OTH exome

AF:

0.000872

GnomAD4 exome

AF:

0.00107

AC:

1557

AN:

1453246

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

746

AN XY:

723000

show subpopulations

Gnomad4 AFR exome

AF:

0.000300

Gnomad4 AMR exome

AF:

0.000540

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000607

Gnomad4 SAS exome

AF:

0.0000816

Gnomad4 FIN exome

AF:

0.0000207

Gnomad4 NFE exome

AF:

0.00127

Gnomad4 OTH exome

AF:

0.00137

GnomAD4 genome

AF:

0.000742

AC:

113

AN:

152268

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000582

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00113

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00112

Hom.:

Bravo

AF:

0.000842

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000694

AC:

ESP6500EA

AF:

0.000941

AC:

ExAC

AF:

0.000468

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

CADD

Benign

0.22

DANN

Benign

0.80

DEOGEN2

Benign

0.025

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.35

M_CAP

Benign

0.014

MetaRNN

Benign

0.0065

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.34

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.25

REVEL

Benign

0.10

Sift

Benign

0.83

Sift4G

Benign

0.62

Polyphen

0.0

Vest4

0.046

MVP

0.43

MPC

0.21

ClinPred

0.0023

GERP RS

-3.9

Varity_R

0.030

gMVP

0.32

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