rs4988484

Positions:

• chr16-1079023-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001172560.3(SSTR5):​c.155C>T​(p.Ala52Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 1,604,336 control chromosomes in the GnomAD database, including 3,027 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. A52A) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.072 (596 hom., cov: 33)
  • Exomes 𝑓: 0.048 (2431 hom.)
• Consequence: SSTR5 NM_001172560.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001693666).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SSTR5	NM_001172560.3	c.155C>T	p.Ala52Val	missense_variant	2/2	ENST00000689027.1
SSTR5	NM_001053.4	c.155C>T	p.Ala52Val	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SSTR5	ENST00000689027.1	c.155C>T	p.Ala52Val	missense_variant	2/2		NM_001172560.3	P1
SSTR5	ENST00000293897.7	c.155C>T	p.Ala52Val	missense_variant	1/1			P1
SSTR5	ENST00000711615.1	c.155C>T	p.Ala52Val	missense_variant	2/2			P1
SSTR5	ENST00000711616.1	c.155C>T	p.Ala52Val	missense_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.0719 AC: 10945 AN: 152172 Hom.: 597 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0461

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0304

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0432

Gnomad OTH AF: 0.0684

GnomAD3 exomes AF: 0.0553 AC: 12892 AN: 233314 Hom.: 613 AF XY: 0.0592 AC XY: 7526 AN XY: 127076

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.0251

Gnomad ASJ exome AF: 0.0563

Gnomad EAS exome AF: 0.000993

Gnomad SAS exome AF: 0.138

Gnomad FIN exome AF: 0.0327

Gnomad NFE exome AF: 0.0421

Gnomad OTH exome AF: 0.0474

GnomAD4 exome AF: 0.0482 AC: 69951 AN: 1452048 Hom.: 2431 Cov.: 30 AF XY: 0.0509 AC XY: 36772 AN XY: 721918

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.0284

Gnomad4 ASJ exome AF: 0.0592

Gnomad4 EAS exome AF: 0.000435

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.0333

Gnomad4 NFE exome AF: 0.0407

Gnomad4 OTH exome AF: 0.0539

GnomAD4 genome AF: 0.0719 AC: 10956 AN: 152288 Hom.: 596 Cov.: 33 AF XY: 0.0710 AC XY: 5286 AN XY: 74466

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0461

Gnomad4 ASJ AF: 0.0539

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0304

Gnomad4 NFE AF: 0.0432

Gnomad4 OTH AF: 0.0667

Alfa AF: 0.0457 Hom.: 179

Bravo AF: 0.0738

TwinsUK AF: 0.0445 AC: 165

ALSPAC AF: 0.0402 AC: 155

ESP6500AA AF: 0.135 AC: 590

ESP6500EA AF: 0.0391 AC: 335

ExAC AF: 0.0574 AC: 6906

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.4
DANN	Benign	0.68
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.85	D
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.40	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.037
Sift	Benign	0.93	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.021
MPC		0.22
ClinPred		0.0055	T
GERP RS		-1.7
Varity_R		0.067
gMVP		0.17

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: rs4988484; hg19: chr16-1129023;