rs139383107

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-1078984-G-A
• chr16-1078984-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001172560.3(SSTR5):​c.116G>A​(p.Arg39Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,589,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: SSTR5 NM_001172560.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09731239).
• BS2: High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SSTR5	NM_001172560.3	c.116G>A	p.Arg39Gln	missense_variant	Exon 2 of 2	ENST00000689027.1	NP_001166031.1
SSTR5	NM_001053.4	c.116G>A	p.Arg39Gln	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>A	p.Arg39Gln	missense_variant	Exon 2 of 2		NM_001172560.3	ENSP00000508487.1
SSTR5	ENST00000293897.6	c.116G>A	p.Arg39Gln	missense_variant	Exon 1 of 1	6		ENSP00000293897.4

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000169 AC: 34 AN: 201750 Hom.: 0 AF XY: 0.000199 AC XY: 22 AN XY: 110564

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000303

Gnomad ASJ exome AF: 0.000108

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000323

Gnomad FIN exome AF: 0.0000636

Gnomad NFE exome AF: 0.000160

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000211 AC: 303 AN: 1437202 Hom.: 0 Cov.: 29 AF XY: 0.000237 AC XY: 169 AN XY: 713662

Gnomad4 AFR exome AF: 0.0000305

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.0000388

Gnomad4 EAS exome AF: 0.0000527

Gnomad4 SAS exome AF: 0.000391

Gnomad4 FIN exome AF: 0.0000627

Gnomad4 NFE exome AF: 0.000215

Gnomad4 OTH exome AF: 0.000236

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152216 Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8 AN XY: 74366

Gnomad4 AFR AF: 0.0000965

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.000112 Hom.: 0

Bravo AF: 0.000125

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000353 AC: 3

ExAC AF: 0.000169 AC: 20

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.116G>A (p.R39Q) alteration is located in exon 1 (coding exon 1) of the SSTR5 gene. This alteration results from a G to A substitution at nucleotide position 116, causing the arginine (R) at amino acid position 39 to be replaced by a glutamine (Q). 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	Benign	0.13
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.078
Sift	Benign	0.28	T
Sift4G	Benign	0.64	T
Polyphen		0.96	D
Vest4		0.11
MVP		0.62
MPC		0.26
ClinPred		0.032	T
GERP RS		3.3
Varity_R		0.069
gMVP		0.25

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;