16-1079270-C-T

Variant names:

• chr16-1079270-C-T
• rs34654948
• NM_001172560.3:c.402C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001172560.3(SSTR5):​c.402C>T​(p.Ser134Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,612,170 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (15 hom., cov: 34)
  • Exomes 𝑓: 0.0010 (24 hom.)
• Consequence: SSTR5 NM_001172560.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.447

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 16-1079270-C-T is Benign according to our data. Variant chr16-1079270-C-T is described in ClinVar as [Benign]. Clinvar id is 790162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.447 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00687 (1047/152346) while in subpopulation AFR AF= 0.0238 (990/41584). AF 95% confidence interval is 0.0226. There are 15 homozygotes in gnomad4. There are 518 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1047 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSTR5	NM_001172560.3	c.402C>T	p.Ser134Ser	synonymous_variant	Exon 2 of 2	ENST00000689027.1	NP_001166031.1
SSTR5	NM_001053.4	c.402C>T	p.Ser134Ser	synonymous_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.402C>T	p.Ser134Ser	synonymous_variant	Exon 2 of 2		NM_001172560.3	ENSP00000508487.1
SSTR5	ENST00000293897.6	c.402C>T	p.Ser134Ser	synonymous_variant	Exon 1 of 1	6		ENSP00000293897.4

Frequencies

GnomAD3 genomes AF: 0.00683 AC: 1040 AN: 152228 Hom.: 15 Cov.: 34

Gnomad AFR AF: 0.0237

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00193 AC: 479 AN: 248382 Hom.: 6 AF XY: 0.00148 AC XY: 200 AN XY: 135020

Gnomad AFR exome AF: 0.0249

Gnomad AMR exome AF: 0.000956

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000385

Gnomad OTH exome AF: 0.000823

GnomAD4 exome AF: 0.00103 AC: 1497 AN: 1459824 Hom.: 24 Cov.: 30 AF XY: 0.000910 AC XY: 661 AN XY: 726192

Gnomad4 AFR exome AF: 0.0274

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000352

Gnomad4 OTH exome AF: 0.00200

GnomAD4 genome AF: 0.00687 AC: 1047 AN: 152346 Hom.: 15 Cov.: 34 AF XY: 0.00695 AC XY: 518 AN XY: 74490

Gnomad4 AFR AF: 0.0238

Gnomad4 AMR AF: 0.00189

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00614

Alfa AF: 0.00207 Hom.: 1

Bravo AF: 0.00770

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

SSTR5-related disorder Benign:1

Jan 06, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	8.1
DANN	Benign	0.80

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: rs34654948; hg19: chr16-1129270;