16-1079193-C-T

Variant names:

• chr16-1079193-C-T
• rs4988487
• NM_001172560.3:c.325C>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.325C>T​(p.Pro109Ser) 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 1,612,536 control chromosomes in the GnomAD database, including 2,753 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.065 (471 hom., cov: 33)
  • Exomes 𝑓: 0.047 (2282 hom.)
• Consequence: SSTR5 NM_001172560.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411
• Publications: 18 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=0.0021184683).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSTR5	NM_001172560.3	c.325C>T	p.Pro109Ser	missense_variant	Exon 2 of 2	ENST00000689027.1	NP_001166031.1
SSTR5	NM_001053.4	c.325C>T	p.Pro109Ser	missense_variant	Exon 1 of 1		NP_001044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SSTR5	ENST00000689027.1	c.325C>T	p.Pro109Ser	missense_variant	Exon 2 of 2		NM_001172560.3	ENSP00000508487.1
SSTR5	ENST00000293897.7	c.325C>T	p.Pro109Ser	missense_variant	Exon 1 of 1	6		ENSP00000293897.4
SSTR5	ENST00000711615.1	c.325C>T	p.Pro109Ser	missense_variant	Exon 2 of 2			ENSP00000518810.1
SSTR5	ENST00000711616.1	c.325C>T	p.Pro109Ser	missense_variant	Exon 1 of 2			ENSP00000518811.1

Frequencies

GnomAD3 genomes AF: 0.0653 AC: 9933 AN: 152208 Hom.: 472 Cov.: 33

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.0545

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0432

Gnomad OTH AF: 0.0635

GnomAD2 exomes AF: 0.0527 AC: 13152 AN: 249364 AF XY: 0.0567

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.0243

Gnomad ASJ exome AF: 0.0586

Gnomad EAS exome AF: 0.000872

Gnomad FIN exome AF: 0.0330

Gnomad NFE exome AF: 0.0419

Gnomad OTH exome AF: 0.0474

GnomAD4 exome AF: 0.0472 AC: 68984 AN: 1460210 Hom.: 2282 Cov.: 30 AF XY: 0.0500 AC XY: 36296 AN XY: 726430

African (AFR) AF: 0.126 AC: 4231 AN: 33474

American (AMR) AF: 0.0275 AC: 1228 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0611 AC: 1595 AN: 26120

East Asian (EAS) AF: 0.000403 AC: 16 AN: 39690

South Asian (SAS) AF: 0.131 AC: 11290 AN: 86254

European-Finnish (FIN) AF: 0.0336 AC: 1744 AN: 51922

Middle Eastern (MID) AF: 0.0766 AC: 442 AN: 5768

European-Non Finnish (NFE) AF: 0.0407 AC: 45286 AN: 1111906

Other (OTH) AF: 0.0522 AC: 3152 AN: 60360

GnomAD4 genome AF: 0.0653 AC: 9943 AN: 152326 Hom.: 471 Cov.: 33 AF XY: 0.0643 AC XY: 4785 AN XY: 74474

African (AFR) AF: 0.121 AC: 5024 AN: 41570

American (AMR) AF: 0.0440 AC: 673 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0545 AC: 189 AN: 3470

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

South Asian (SAS) AF: 0.129 AC: 623 AN: 4824

European-Finnish (FIN) AF: 0.0303 AC: 322 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0432 AC: 2941 AN: 68026

Other (OTH) AF: 0.0619 AC: 131 AN: 2116

Alfa AF: 0.0469 Hom.: 307

Bravo AF: 0.0666

TwinsUK AF: 0.0442 AC: 164

ALSPAC AF: 0.0402 AC: 155

ESP6500AA AF: 0.115 AC: 505

ESP6500EA AF: 0.0394 AC: 339

ExAC AF: 0.0566 AC: 6835

Asia WGS AF: 0.0490 AC: 171 AN: 3478

EpiCase AF: 0.0411

EpiControl AF: 0.0453

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.86
DANN	Benign	0.89
DEOGEN2	Benign	0.067	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.058	N
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		-0.41
PrimateAI	Benign	0.28	T
PROVEAN	Benign	2.6	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.034
MPC		0.23
ClinPred		0.00028	T
GERP RS		0.41
PromoterAI		-0.012	Neutral
Varity_R		0.049
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: rs4988487; hg19: chr16-1129193; COSMIC: COSV53511451; COSMIC: COSV53511451;