rs540162038

Variant names:

• chr16-1079088-G-A
• rs540162038
• NM_001172560.3:c.220G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001172560.3(SSTR5):​c.220G>A​(p.Val74Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000291 in 1,612,616 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: 𝑓 0.000033 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: SSTR5 NM_001172560.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.50
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.36653358).
• BS2: High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172560.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSTR5	NM_001172560.3	MANE Select	c.220G>A	p.Val74Ile	missense	Exon 2 of 2	NP_001166031.1	P35346
	SSTR5	NM_001053.4		c.220G>A	p.Val74Ile	missense	Exon 1 of 1	NP_001044.1	P35346

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSTR5	ENST00000689027.1	MANE Select	c.220G>A	p.Val74Ile	missense	Exon 2 of 2	ENSP00000508487.1	P35346
	SSTR5	ENST00000293897.7	TSL:6	c.220G>A	p.Val74Ile	missense	Exon 1 of 1	ENSP00000293897.4	P35346
	SSTR5	ENST00000711615.1		c.220G>A	p.Val74Ile	missense	Exon 2 of 2	ENSP00000518810.1	P35346

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152204 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 249590 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000288 AC: 42 AN: 1460294 Hom.: 0 Cov.: 30 AF XY: 0.0000248 AC XY: 18 AN XY: 726458

African (AFR) AF: 0.0000896 AC: 3 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26124

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52022

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000297 AC: 33 AN: 1111904

Other (OTH) AF: 0.0000497 AC: 3 AN: 60354

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152322 Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3 AN XY: 74480

African (AFR) AF: 0.0000241 AC: 1 AN: 41564

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000762 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000248 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		5.5
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.26
Sift	Benign	0.24	T
Sift4G	Benign	0.12	T
Polyphen		0.99	D
Vest4		0.16
MutPred		0.79		Loss of catalytic residue at V74 (P = 0.1459)
MVP		0.45
MPC		0.56
ClinPred		0.21	T
GERP RS		4.9
PromoterAI		-0.021	Neutral
Varity_R		0.30
gMVP		0.39
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs540162038; hg19: chr16-1129088;