rs4988483

Positions:

• chr16-1079010-C-A

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

• Frequency:
  • Genomes: 𝑓 0.037 (144 hom., cov: 33)
  • Exomes 𝑓: 0.050 (2055 hom.)
• Consequence: SSTR5 NM_001172560.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0830

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=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	c.142C>A	p.Leu48Met	missense_variant	2/2	ENST00000689027.1	NP_001166031.1
SSTR5	NM_001053.4	c.142C>A	p.Leu48Met	missense_variant	1/1		NP_001044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSTR5	ENST00000689027.1	c.142C>A	p.Leu48Met	missense_variant	2/2		NM_001172560.3	ENSP00000508487	P1
SSTR5	ENST00000293897.7	c.142C>A	p.Leu48Met	missense_variant	1/1			ENSP00000293897	P1
SSTR5	ENST00000711615.1	c.142C>A	p.Leu48Met	missense_variant	2/2			ENSP00000518810	P1
SSTR5	ENST00000711616.1	c.142C>A	p.Leu48Met	missense_variant	1/2			ENSP00000518811

Frequencies

GnomAD3 genomes AF: 0.0369 AC: 5615 AN: 152218 Hom.: 143 Cov.: 33

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

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.: 30 AF XY: 0.0493 AC XY: 35515 AN XY: 720492

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.: 33 AF XY: 0.0349 AC XY: 2598 AN XY: 74492

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: 50

ESP6500EA AF: 0.0548 AC: 470

ExAC AF: 0.0346 AC: 4153

Asia WGS AF: 0.00722 AC: 25 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: 12192619, 21744088, 19423539, 21692047) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.0064
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	0.94	D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.091
Sift	Benign	0.11	T
Sift4G	Benign	0.21	T
Polyphen		0.93	P
Vest4		0.14
MPC		0.81
ClinPred		0.010	T
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

Other links and lift over

dbSNP: rs4988483; hg19: chr16-1129010; COSMIC: COSV53512216; COSMIC: COSV53512216;