chr16-1078894-C-G

Variant names:

• chr16-1078894-C-G
• rs143790659
• NM_001172560.3:c.26C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001172560.3(SSTR5):​c.26C>G​(p.Thr9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T9M) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SSTR5 NM_001172560.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38
• Publications: 2 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]

SSTR5-AS1 (HGNC:26502): (SSTR5 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05861771).

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.26C>G	p.Thr9Arg	missense	Exon 2 of 2	NP_001166031.1	P35346
	SSTR5	NM_001053.4		c.26C>G	p.Thr9Arg	missense	Exon 1 of 1	NP_001044.1	P35346
	SSTR5-AS1	NR_027242.1		n.-163G>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSTR5	ENST00000689027.1	MANE Select	c.26C>G	p.Thr9Arg	missense	Exon 2 of 2	ENSP00000508487.1	P35346
	SSTR5	ENST00000293897.7	TSL:6	c.26C>G	p.Thr9Arg	missense	Exon 1 of 1	ENSP00000293897.4	P35346
	SSTR5	ENST00000711615.1		c.26C>G	p.Thr9Arg	missense	Exon 2 of 2	ENSP00000518810.1	P35346

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000427 AC: 1 AN: 234020 AF XY: 0.00000775

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000952

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454140 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 723564

African (AFR) AF: 0.00 AC: 0 AN: 33402

American (AMR) AF: 0.00 AC: 0 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 85970

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47898

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5352

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111120

Other (OTH) AF: 0.00 AC: 0 AN: 60106

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000835 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.060
DANN	Benign	0.51
DEOGEN2	Benign	0.077	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.064	D
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PhyloP100		-2.4
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.12
Sift	Benign	0.39	T
Sift4G	Benign	0.49	T
Polyphen		0.0010	B
Vest4		0.092
MutPred		0.17		Loss of glycosylation at T9 (P = 0.0046)
MVP		0.31
MPC		0.25
ClinPred		0.037	T
GERP RS		-6.4
PromoterAI		0.050	Neutral
Varity_R		0.071
gMVP		0.55

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: rs143790659; hg19: chr16-1128894;