rs642249

Positions:

• chr16-1079912-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001172560.3(SSTR5):​c.1044A>G​(p.Pro348Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.964 in 1,606,566 control chromosomes in the GnomAD database, including 747,450 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.96 (69747 hom., cov: 36)
  • Exomes 𝑓: 0.96 (677703 hom.)
• Consequence: SSTR5 NM_001172560.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 16-1079912-A-G is Benign according to our data. Variant chr16-1079912-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.177 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SSTR5	NM_001172560.3	c.1044A>G	p.Pro348Pro	synonymous_variant	2/2	ENST00000689027.1	NP_001166031.1
SSTR5	NM_001053.4	c.1044A>G	p.Pro348Pro	synonymous_variant	1/1		NP_001044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SSTR5	ENST00000689027.1	c.1044A>G	p.Pro348Pro	synonymous_variant	2/2		NM_001172560.3	ENSP00000508487.1
SSTR5	ENST00000293897.6	c.1044A>G	p.Pro348Pro	synonymous_variant	1/1	6		ENSP00000293897.4

Frequencies

GnomAD3 genomes AF: 0.957 AC: 145614 AN: 152216 Hom.: 69705 Cov.: 36

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.961

Gnomad AMR AF: 0.981

Gnomad ASJ AF: 0.981

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.966

Gnomad OTH AF: 0.968

GnomAD3 exomes AF: 0.956 AC: 226852 AN: 237238 Hom.: 108661 AF XY: 0.953 AC XY: 123591 AN XY: 129734

Gnomad AFR exome AF: 0.932

Gnomad AMR exome AF: 0.987

Gnomad ASJ exome AF: 0.977

Gnomad EAS exome AF: 0.931

Gnomad SAS exome AF: 0.879

Gnomad FIN exome AF: 0.972

Gnomad NFE exome AF: 0.970

Gnomad OTH exome AF: 0.967

GnomAD4 exome AF: 0.965 AC: 1403240 AN: 1454232 Hom.: 677703 Cov.: 76 AF XY: 0.962 AC XY: 695749 AN XY: 723110

Gnomad4 AFR exome AF: 0.932

Gnomad4 AMR exome AF: 0.986

Gnomad4 ASJ exome AF: 0.978

Gnomad4 EAS exome AF: 0.954

Gnomad4 SAS exome AF: 0.882

Gnomad4 FIN exome AF: 0.973

Gnomad4 NFE exome AF: 0.971

Gnomad4 OTH exome AF: 0.961

GnomAD4 genome AF: 0.957 AC: 145709 AN: 152334 Hom.: 69747 Cov.: 36 AF XY: 0.956 AC XY: 71183 AN XY: 74480

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.981

Gnomad4 ASJ AF: 0.981

Gnomad4 EAS AF: 0.932

Gnomad4 SAS AF: 0.880

Gnomad4 FIN AF: 0.969

Gnomad4 NFE AF: 0.966

Gnomad4 OTH AF: 0.961

Alfa AF: 0.966 Hom.: 24484

Bravo AF: 0.960

Asia WGS AF: 0.890 AC: 3094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs642249; hg19: chr16-1129912; COSMIC: COSV53511767; COSMIC: COSV53511767;