rs4988484

Variant names:

• chr16-1079023-C-T
• rs4988484
• NM_001172560.3:c.155C>T

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172560.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSTR5	NM_001172560.3	MANE Select	c.155C>T	p.Ala52Val	missense	Exon 2 of 2	NP_001166031.1	P35346
	SSTR5	NM_001053.4		c.155C>T	p.Ala52Val	missense	Exon 1 of 1	NP_001044.1	P35346

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSTR5	ENST00000689027.1	MANE Select	c.155C>T	p.Ala52Val	missense	Exon 2 of 2	ENSP00000508487.1	P35346
	SSTR5	ENST00000293897.7	TSL:6	c.155C>T	p.Ala52Val	missense	Exon 1 of 1	ENSP00000293897.4	P35346
	SSTR5	ENST00000711615.1		c.155C>T	p.Ala52Val	missense	Exon 2 of 2	ENSP00000518810.1	P35346

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

GnomAD2 exomes AF: 0.0553 AC: 12892 AN: 233314 AF XY: 0.0592

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 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

African (AFR) AF: 0.151 AC: 5031 AN: 33216

American (AMR) AF: 0.0284 AC: 1236 AN: 43476

Ashkenazi Jewish (ASJ) AF: 0.0592 AC: 1541 AN: 26010

East Asian (EAS) AF: 0.000435 AC: 17 AN: 39040

South Asian (SAS) AF: 0.136 AC: 11654 AN: 85534

European-Finnish (FIN) AF: 0.0333 AC: 1687 AN: 50606

Middle Eastern (MID) AF: 0.0764 AC: 438 AN: 5736

European-Non Finnish (NFE) AF: 0.0407 AC: 45111 AN: 1108434

Other (OTH) AF: 0.0539 AC: 3236 AN: 59996

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

African (AFR) AF: 0.144 AC: 5988 AN: 41538

American (AMR) AF: 0.0461 AC: 706 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0539 AC: 187 AN: 3472

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5186

South Asian (SAS) AF: 0.131 AC: 632 AN: 4828

European-Finnish (FIN) AF: 0.0304 AC: 323 AN: 10628

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0432 AC: 2939 AN: 68016

Other (OTH) AF: 0.0667 AC: 141 AN: 2114

Alfa AF: 0.0479 Hom.: 265

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 v4.9

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
PhyloP100		0.19
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
PromoterAI		0.00040	Neutral
Varity_R		0.067
gMVP		0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4988484; hg19: chr16-1129023;