NM_001172560.3:c.1069G>A

Variant names:

• chr16-1079937-G-A
• rs34947461
• NM_001172560.3:c.1069G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001172560.3(SSTR5):​c.1069G>A​(p.Gly357Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,603,934 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 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: 𝑓 0.0011 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0015 (2 hom.)
• Consequence: SSTR5 NM_001172560.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 8 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013089985).
• BS2: High AC in GnomAd4 at 162 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSTR5	NM_001172560.3	MANE Select	c.1069G>A	p.Gly357Arg	missense	Exon 2 of 2	NP_001166031.1
	SSTR5	NM_001053.4		c.1069G>A	p.Gly357Arg	missense	Exon 1 of 1	NP_001044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSTR5	ENST00000689027.1	MANE Select	c.1069G>A	p.Gly357Arg	missense	Exon 2 of 2	ENSP00000508487.1
	SSTR5	ENST00000293897.7	TSL:6	c.1069G>A	p.Gly357Arg	missense	Exon 1 of 1	ENSP00000293897.4
	SSTR5	ENST00000711615.1		c.1069G>A	p.Gly357Arg	missense	Exon 2 of 2	ENSP00000518810.1

Frequencies

GnomAD3 genomes AF: 0.00106 AC: 161 AN: 152250 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00159

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00121 AC: 277 AN: 229862 AF XY: 0.00119

Gnomad AFR exome AF: 0.000291

Gnomad AMR exome AF: 0.000788

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000262

Gnomad NFE exome AF: 0.00218

Gnomad OTH exome AF: 0.000712

GnomAD4 exome AF: 0.00152 AC: 2205 AN: 1451566 Hom.: 2 Cov.: 33 AF XY: 0.00145 AC XY: 1049 AN XY: 721186

African (AFR) AF: 0.000210 AC: 7 AN: 33304

American (AMR) AF: 0.000825 AC: 36 AN: 43658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25782

East Asian (EAS) AF: 0.00 AC: 0 AN: 39426

South Asian (SAS) AF: 0.000598 AC: 51 AN: 85278

European-Finnish (FIN) AF: 0.000236 AC: 12 AN: 50910

Middle Eastern (MID) AF: 0.000354 AC: 2 AN: 5656

European-Non Finnish (NFE) AF: 0.00183 AC: 2029 AN: 1107646

Other (OTH) AF: 0.00114 AC: 68 AN: 59906

GnomAD4 genome AF: 0.00106 AC: 162 AN: 152368 Hom.: 0 Cov.: 34 AF XY: 0.00105 AC XY: 78 AN XY: 74510

African (AFR) AF: 0.000361 AC: 15 AN: 41582

American (AMR) AF: 0.00216 AC: 33 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10632

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

European-Non Finnish (NFE) AF: 0.00159 AC: 108 AN: 68032

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00154 Hom.: 2

Bravo AF: 0.00117

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00182 AC: 7

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00130 AC: 11

ExAC AF: 0.00142 AC: 170

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Benign	0.91
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	0.81	L
PhyloP100		1.4
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.20
Sift	Uncertain	0.020	D
Sift4G	Benign	0.097	T
Polyphen		0.12	B
Vest4		0.19
MutPred		0.13		Gain of solvent accessibility (P = 0.019)
MVP		0.73
MPC		0.29
ClinPred		0.028	T
GERP RS		1.7
Varity_R		0.13
gMVP		0.62
Mutation Taster		=72/28	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: rs34947461; hg19: chr16-1129937; COSMIC: COSV104541501; COSMIC: COSV104541501;