16-1079082-A-G

Variant names:

• chr16-1079082-A-G
• rs755773123
• NM_001172560.3:c.214A>G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001172560.3(SSTR5):​c.214A>G​(p.Lys72Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,460,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: SSTR5 NM_001172560.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.85

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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.34709778).
• BS2: High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSTR5	NM_001172560.3	c.214A>G	p.Lys72Glu	missense_variant	Exon 2 of 2	ENST00000689027.1	NP_001166031.1
SSTR5	NM_001053.4	c.214A>G	p.Lys72Glu	missense_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.214A>G	p.Lys72Glu	missense_variant	Exon 2 of 2		NM_001172560.3	ENSP00000508487.1
SSTR5	ENST00000293897.6	c.214A>G	p.Lys72Glu	missense_variant	Exon 1 of 1	6		ENSP00000293897.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249586 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135544

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000822 AC: 12 AN: 1460330 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 726472

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000899

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000828 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.214A>G (p.K72E) alteration is located in exon 1 (coding exon 1) of the SSTR5 gene. This alteration results from a A to G substitution at nucleotide position 214, causing the lysine (K) at amino acid position 72 to be replaced by a glutamic acid (E). 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	Pathogenic	0.62
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.23
Sift	Benign	0.14	T
Sift4G	Benign	0.20	T
Polyphen		0.85	P
Vest4		0.18
MutPred		0.64		Loss of MoRF binding (P = 0.0404);
MVP		0.63
MPC		0.79
ClinPred		0.59	D
GERP RS		3.8
Varity_R		0.24
gMVP		0.65

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: rs755773123; hg19: chr16-1129082;