16-1078987-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001172560.3(SSTR5):c.119C>T(p.Ala40Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000604 in 1,590,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000064 (0 hom.)
• Consequence: SSTR5 NM_001172560.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.97

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13974962).
• BS2: High AC in GnomAdExome at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SSTR5	NM_001172560.3	c.119C>T	p.Ala40Val	missense_variant	2/2	ENST00000689027.1
SSTR5	NM_001053.4	c.119C>T	p.Ala40Val	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SSTR5	ENST00000689027.1	c.119C>T	p.Ala40Val	missense_variant	2/2		NM_001172560.3	P1
SSTR5	ENST00000293897.7	c.119C>T	p.Ala40Val	missense_variant	1/1			P1
SSTR5	ENST00000711615.1	c.119C>T	p.Ala40Val	missense_variant	2/2			P1
SSTR5	ENST00000711616.1	c.119C>T	p.Ala40Val	missense_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152218 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000834 AC: 17 AN: 203762 Hom.: 0 AF XY: 0.0000717 AC XY: 8 AN XY: 111534

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000267

Gnomad ASJ exome AF: 0.000323

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000676

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000640 AC: 92 AN: 1438400 Hom.: 0 Cov.: 29 AF XY: 0.0000616 AC XY: 44 AN XY: 714370

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000242

Gnomad4 ASJ exome AF: 0.000697

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000526

Gnomad4 OTH exome AF: 0.000101

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152218 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74366

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000136 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.0000504 AC: 6

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2023

The c.119C>T (p.A40V) alteration is located in exon 1 (coding exon 1) of the SSTR5 gene. This alteration results from a C to T substitution at nucleotide position 119, causing the alanine (A) at amino acid position 40 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	19
Dann	Uncertain	1.0
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.10
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.026	D
Polyphen		0.80	P
Vest4		0.091
MutPred		0.53		Gain of helix (P = 0.062);
MVP		0.52
MPC		0.22
ClinPred		0.069	T
GERP RS		4.6
Varity_R		0.14
gMVP		0.37

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: rs752514090; hg19: chr16-1128987; COSMIC: COSV53511309; COSMIC: COSV53511309;