16-1079193-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001172560.3(SSTR5):​c.325C>A​(p.Pro109Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052247882).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSTR5	NM_001172560.3	MANE Select	c.325C>A	p.Pro109Thr	missense	Exon 2 of 2	NP_001166031.1
	SSTR5	NM_001053.4		c.325C>A	p.Pro109Thr	missense	Exon 1 of 1	NP_001044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSTR5	ENST00000689027.1	MANE Select	c.325C>A	p.Pro109Thr	missense	Exon 2 of 2	ENSP00000508487.1
	SSTR5	ENST00000293897.7	TSL:6	c.325C>A	p.Pro109Thr	missense	Exon 1 of 1	ENSP00000293897.4
	SSTR5	ENST00000711615.1		c.325C>A	p.Pro109Thr	missense	Exon 2 of 2	ENSP00000518810.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249364 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000891

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460218 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726430

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51926

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111910

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000829 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.4
DANN	Benign	0.90
DEOGEN2	Benign	0.070	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.61	N
PhyloP100		-0.41
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.048
Sift	Benign	0.21	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.044
MutPred		0.24		Loss of loop (P = 0.2237)
MVP		0.66
MPC		0.36
ClinPred		0.029	T
GERP RS		0.41
PromoterAI		-0.015	Neutral
Varity_R		0.080
gMVP		0.20

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;