Variant 16-1079010-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001172560.3(SSTR5):c.142C>A(p.Leu48Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0489 in 1,601,838 control chromosomes in the GnomAD database, including 2,199 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.037 ( 144 hom., cov: 33)

Exomes 𝑓: 0.050 ( 2055 hom. )

Consequence

SSTR5
NM_001172560.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0830

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033727884).

BP6

Variant 16-1079010-C-A is Benign according to our data. Variant chr16-1079010-C-A is described in ClinVar as [Benign]. Clinvar id is 1224021.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSTR5	NM_001172560.3 link	c.142C>A	p.Leu48Met	missense_variant	2/2	ENST00000689027.1	NP_001166031.1	P35346
SSTR5	NM_001053.4 link	c.142C>A	p.Leu48Met	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.142C>A	p.Leu48Met	missense_variant	2/2		NM_001172560.3	ENSP00000508487.1		P35346
SSTR5	ENST00000293897.6 link	c.142C>A	p.Leu48Met	missense_variant	1/1	6		ENSP00000293897.4		P35346

Frequencies

GnomAD3 genomes

AF:

0.0369

AC:

5615

AN:

152218

Hom.:

143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0108

Gnomad AMI

AF:

0.0912

Gnomad AMR

AF:

0.0429

Gnomad ASJ

AF:

0.0446

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.0189

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0573

Gnomad OTH

AF:

0.0435

GnomAD3 exomes

AF:

0.0374

AC:

8533

AN:

228194

Hom.:

211

AF XY:

0.0380

AC XY:

4733

AN XY:

124474

show subpopulations

Gnomad AFR exome

AF:

0.00982

Gnomad AMR exome

AF:

0.0280

Gnomad ASJ exome

AF:

0.0408

Gnomad EAS exome

AF:

0.000179

Gnomad SAS exome

AF:

0.0164

Gnomad FIN exome

AF:

0.0203

Gnomad NFE exome

AF:

0.0591

Gnomad OTH exome

AF:

0.0418

GnomAD4 exome

AF:

0.0501

AC:

72672

AN:

1449502

Hom.:

2055

Cov.:

AF XY:

0.0493

AC XY:

35515

AN XY:

720492

show subpopulations

Gnomad4 AFR exome

AF:

0.00880

Gnomad4 AMR exome

AF:

0.0299

Gnomad4 ASJ exome

AF:

0.0447

Gnomad4 EAS exome

AF:

0.000205

Gnomad4 SAS exome

AF:

0.0178

Gnomad4 FIN exome

AF:

0.0199

Gnomad4 NFE exome

AF:

0.0582

Gnomad4 OTH exome

AF:

0.0439

GnomAD4 genome

AF:

0.0369

AC:

5618

AN:

152336

Hom.:

144

Cov.:

AF XY:

0.0349

AC XY:

2598

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.0429

Gnomad4 ASJ

AF:

0.0446

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0149

Gnomad4 FIN

AF:

0.0189

Gnomad4 NFE

AF:

0.0573

Gnomad4 OTH

AF:

0.0430

Alfa

AF:

0.0532

Hom.:

173

Bravo

AF:

0.0377

TwinsUK

AF:

0.0542

AC:

201

ALSPAC

AF:

0.0607

AC:

234

ESP6500AA

AF:

0.0115

AC:

ESP6500EA

AF:

0.0548

AC:

470

ExAC

AF:

0.0346

AC:

4153

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 01, 2020	This variant is associated with the following publications: (PMID: 12192619, 21744088, 19423539, 21692047) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.070

Eigen

Benign

-0.0064

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0034

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.80

REVEL

Benign

0.091

Sift

Benign

0.11

Sift4G

Benign

0.21

Polyphen

0.93

Vest4

0.14

MPC

0.81

ClinPred

0.010

GERP RS

1.4

Varity_R

0.085

gMVP

0.29

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