16-1079872-C-T

Variant names:

Variant summary

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

The NM_001172560.3(SSTR5):c.1004C>T(p.Pro335Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 1,609,844 control chromosomes in the GnomAD database, including 237,566 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 0.50 ( 20002 hom., cov: 35)

Exomes 𝑓: 0.54 ( 217564 hom. )

Consequence

SSTR5
NM_001172560.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.117

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=1.4184657E-6).

BP6

Variant 16-1079872-C-T is Benign according to our data. Variant chr16-1079872-C-T is described in ClinVar as [Benign]. Clinvar id is 1248656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1079872-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSTR5	NM_001172560.3 link	c.1004C>T	p.Pro335Leu	missense_variant	Exon 2 of 2	ENST00000689027.1	NP_001166031.1	P35346
SSTR5	NM_001053.4 link	c.1004C>T	p.Pro335Leu	missense_variant	Exon 1 of 1		NP_001044.1	P35346

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSTR5	ENST00000689027.1 link	c.1004C>T	p.Pro335Leu	missense_variant	Exon 2 of 2		NM_001172560.3	ENSP00000508487.1		P35346
SSTR5	ENST00000293897.6 link	c.1004C>T	p.Pro335Leu	missense_variant	Exon 1 of 1	6		ENSP00000293897.4		P35346

Frequencies

GnomAD3 genomes

AF:

0.502

AC:

76349

AN:

152048

Hom.:

19994

Cov.:

show subpopulations

Gnomad AFR

AF:

0.374

Gnomad AMI

AF:

0.671

Gnomad AMR

AF:

0.503

Gnomad ASJ

AF:

0.613

Gnomad EAS

AF:

0.808

Gnomad SAS

AF:

0.452

Gnomad FIN

AF:

0.603

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.536

Gnomad OTH

AF:

0.512

GnomAD3 exomes

AF:

0.543

AC:

132664

AN:

244142

Hom.:

37123

AF XY:

0.539

AC XY:

71673

AN XY:

132988

show subpopulations

Gnomad AFR exome

AF:

0.371

Gnomad AMR exome

AF:

0.555

Gnomad ASJ exome

AF:

0.581

Gnomad EAS exome

AF:

0.807

Gnomad SAS exome

AF:

0.433

Gnomad FIN exome

AF:

0.592

Gnomad NFE exome

AF:

0.538

Gnomad OTH exome

AF:

0.562

GnomAD4 exome

AF:

0.542

AC:

790044

AN:

1457678

Hom.:

217564

Cov.:

AF XY:

0.539

AC XY:

390848

AN XY:

725198

show subpopulations

Gnomad4 AFR exome

AF:

0.358

Gnomad4 AMR exome

AF:

0.550

Gnomad4 ASJ exome

AF:

0.577

Gnomad4 EAS exome

AF:

0.825

Gnomad4 SAS exome

AF:

0.434

Gnomad4 FIN exome

AF:

0.594

Gnomad4 NFE exome

AF:

0.542

Gnomad4 OTH exome

AF:

0.553

GnomAD4 genome

AF:

0.502

AC:

76397

AN:

152166

Hom.:

20002

Cov.:

AF XY:

0.504

AC XY:

37487

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.375

Gnomad4 AMR

AF:

0.502

Gnomad4 ASJ

AF:

0.613

Gnomad4 EAS

AF:

0.807

Gnomad4 SAS

AF:

0.453

Gnomad4 FIN

AF:

0.603

Gnomad4 NFE

AF:

0.536

Gnomad4 OTH

AF:

0.510

Alfa

AF:

0.538

Hom.:

33117

Bravo

AF:

0.495

TwinsUK

AF:

0.539

AC:

2000

ALSPAC

AF:

0.532

AC:

2052

ESP6500AA

AF:

0.383

AC:

1671

ESP6500EA

AF:

0.539

AC:

4627

ExAC

AF:

0.532

AC:

63977

Asia WGS

AF:

0.620

AC:

2153

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 01, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 21249361) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.070

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.090

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0000014

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.3

REVEL

Benign

0.078

Sift

Benign

0.17

Sift4G

Benign

0.45

Polyphen

0.055

Vest4

0.038

MPC

0.24

ClinPred

0.0048

GERP RS

2.2

Varity_R

0.029

gMVP

0.34

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