16-1079872-C-T

Position:

• chr16-1079872-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.50 (20002 hom., cov: 35)
  • Exomes 𝑓: 0.54 (217564 hom.)
• Consequence: SSTR5 NM_001172560.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.117

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]

ACMG classification

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/exons	MANE	Protein	UniProt
SSTR5	NM_001172560.3	c.1004C>T	p.Pro335Leu	missense_variant	2/2	ENST00000689027.1	NP_001166031.1
SSTR5	NM_001053.4	c.1004C>T	p.Pro335Leu	missense_variant	1/1		NP_001044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSTR5	ENST00000689027.1	c.1004C>T	p.Pro335Leu	missense_variant	2/2		NM_001172560.3	ENSP00000508487.1
SSTR5	ENST00000293897.6	c.1004C>T	p.Pro335Leu	missense_variant	1/1	6		ENSP00000293897.4

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76349 AN: 152048 Hom.: 19994 Cov.: 35

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

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.: 77 AF XY: 0.539 AC XY: 390848 AN XY: 725198

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.: 35 AF XY: 0.504 AC XY: 37487 AN XY: 74410

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

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: 21249361) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.090	N
LIST_S2	Benign	0.55	T
MetaRNN	Benign	0.0000014	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.078
Sift	Benign	0.17	T
Sift4G	Benign	0.45	T
Polyphen		0.055	B
Vest4		0.038
MPC		0.24
ClinPred		0.0048	T
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

Other links and lift over

dbSNP: rs169068; hg19: chr16-1129872; COSMIC: COSV53512141; COSMIC: COSV53512141;