16-1079193-C-T

Variant names:

• chr16-1079193-C-T
• rs4988487
• NM_001172560.3:c.325C>T

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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=0.0021184683).
• 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	ENST00000293897.6	c.325C>T	p.Pro109Ser	missense_variant	Exon 1 of 1	6		ENSP00000293897.4

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

GnomAD3 exomes AF: 0.0527 AC: 13152 AN: 249364 Hom.: 580 AF XY: 0.0567 AC XY: 7687 AN XY: 135478

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 SAS exome AF: 0.132

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

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.0275

Gnomad4 ASJ exome AF: 0.0611

Gnomad4 EAS exome AF: 0.000403

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.0336

Gnomad4 NFE exome AF: 0.0407

Gnomad4 OTH exome AF: 0.0522

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

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.0440

Gnomad4 ASJ AF: 0.0545

Gnomad4 EAS AF: 0.00289

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.0303

Gnomad4 NFE AF: 0.0432

Gnomad4 OTH AF: 0.0619

Alfa AF: 0.0457 Hom.: 201

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
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
Varity_R		0.049
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: rs4988487; hg19: chr16-1129193; COSMIC: COSV53511451; COSMIC: COSV53511451;