16-1079586-C-T

Position:

• chr16-1079586-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001172560.3(SSTR5):​c.718C>T​(p.Arg240Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,611,038 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (9 hom.)
• Consequence: SSTR5 NM_001172560.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.89

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.047788113).
• BP6: Variant 16-1079586-C-T is Benign according to our data. Variant chr16-1079586-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 12874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 188 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSTR5	NM_001172560.3	c.718C>T	p.Arg240Trp	missense_variant	2/2	ENST00000689027.1	NP_001166031.1
SSTR5	NM_001053.4	c.718C>T	p.Arg240Trp	missense_variant	1/1		NP_001044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSTR5	ENST00000689027.1	c.718C>T	p.Arg240Trp	missense_variant	2/2		NM_001172560.3	ENSP00000508487	P1
SSTR5	ENST00000293897.7	c.718C>T	p.Arg240Trp	missense_variant	1/1			ENSP00000293897	P1
SSTR5	ENST00000711615.1	c.718C>T	p.Arg240Trp	missense_variant	2/2			ENSP00000518810	P1
SSTR5	ENST00000711616.1	c.681+37C>T		intron_variant				ENSP00000518811

Frequencies

GnomAD3 genomes AF: 0.00124 AC: 188 AN: 152202 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00156 AC: 384 AN: 246580 Hom.: 1 AF XY: 0.00158 AC XY: 211 AN XY: 133906

Gnomad AFR exome AF: 0.000189

Gnomad AMR exome AF: 0.000378

Gnomad ASJ exome AF: 0.0134

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000658

Gnomad FIN exome AF: 0.000706

Gnomad NFE exome AF: 0.00188

Gnomad OTH exome AF: 0.00183

GnomAD4 exome AF: 0.00137 AC: 1992 AN: 1458718 Hom.: 9 Cov.: 32 AF XY: 0.00139 AC XY: 1008 AN XY: 725494

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000651

Gnomad4 ASJ exome AF: 0.0150

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000163

Gnomad4 FIN exome AF: 0.000786

Gnomad4 NFE exome AF: 0.00124

Gnomad4 OTH exome AF: 0.00216

GnomAD4 genome AF: 0.00123 AC: 188 AN: 152320 Hom.: 1 Cov.: 33 AF XY: 0.00117 AC XY: 87 AN XY: 74480

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00143

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00204 Hom.: 3

Bravo AF: 0.00140

ESP6500AA AF: 0.000686 AC: 3

ESP6500EA AF: 0.00210 AC: 18

ExAC AF: 0.00163 AC: 196

EpiCase AF: 0.00125

EpiControl AF: 0.00148

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	SSTR5: BS2 -
Benign, no assertion criteria provided	literature only	OMIM	Aug 01, 2001	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.57	T
MutationAssessor	Pathogenic	3.4	M
MutationTaster	Benign	0.98	A;A;A
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-6.6	D
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.84
MVP		0.72
MPC		0.84
ClinPred		0.073	T
GERP RS		2.6
Varity_R		0.73
gMVP		0.76

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: rs121917877; hg19: chr16-1129586;