chr16-1078984-G-C

Variant names:

• chr16-1078984-G-C
• rs139383107
• NM_001172560.3:c.116G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001172560.3(SSTR5):​c.116G>C​(p.Arg39Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,437,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SSTR5 NM_001172560.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.472

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38853234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSTR5	NM_001172560.3	c.116G>C	p.Arg39Pro	missense_variant	Exon 2 of 2	ENST00000689027.1	NP_001166031.1
SSTR5	NM_001053.4	c.116G>C	p.Arg39Pro	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.116G>C	p.Arg39Pro	missense_variant	Exon 2 of 2		NM_001172560.3	ENSP00000508487.1
SSTR5	ENST00000293897.6	c.116G>C	p.Arg39Pro	missense_variant	Exon 1 of 1	6		ENSP00000293897.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1437202 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 713662

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.07e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.062	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.21
Sift	Benign	0.14	T
Sift4G	Benign	0.34	T
Polyphen		0.92	P
Vest4		0.39
MutPred		0.57		Gain of sheet (P = 0.0028);
MVP		0.66
MPC		0.32
ClinPred		0.19	T
GERP RS		3.3
Varity_R		0.44
gMVP		0.73

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: rs139383107; hg19: chr16-1128984;