22-37206803-C-A

Variant names:

• chr22-37206803-C-A
• rs139709130
• NM_001051.5:c.1001G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001051.5(SSTR3):​c.1001G>T​(p.Arg334Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,980 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R334H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SSTR3 NM_001051.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62
• Publications: 0 publications found

Genes affected

SSTR3 (HGNC:11332): (somatostatin receptor 3) This gene encodes a member of the somatostatin receptor protein family. Somatostatins are peptide hormones that regulate diverse cellular functions such as neurotransmission, cell proliferation, and endocrine signaling as well as inhibiting the release of many hormones and other secretory proteins. Somatostatin has two active forms of 14 and 28 amino acids. The biological effects of somatostatins are mediated by a family of G-protein coupled somatostatin receptors that are expressed in a tissue-specific manner. Somatostatin receptors form homodimers and heterodimers with other members of the superfamily as well as with other G-protein coupled receptors and receptor tyrosine kinases. This protein is functionally coupled to adenylyl cyclase. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001051.5. 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
	SSTR3	NM_001051.5	MANE Select	c.1001G>T	p.Arg334Leu	missense	Exon 2 of 2	NP_001042.1	P32745
	SSTR3	NM_001278687.2		c.1001G>T	p.Arg334Leu	missense	Exon 2 of 2	NP_001265616.1	P32745

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SSTR3	ENST00000610913.2	TSL:1 MANE Select	c.1001G>T	p.Arg334Leu	missense	Exon 2 of 2	ENSP00000480971.1	P32745
	SSTR3	ENST00000617123.1	TSL:1	c.1001G>T	p.Arg334Leu	missense	Exon 2 of 2	ENSP00000481325.1	P32745
	SSTR3	ENST00000959749.1		c.1001G>T	p.Arg334Leu	missense	Exon 3 of 3	ENSP00000629808.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459980 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726360

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51680

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111896

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.97	L
PhyloP100		2.6
PrimateAI	Uncertain	0.52	T
Sift4G	Benign	0.13	T
Polyphen		0.99	D
Vest4		0.53
MutPred		0.47		Loss of MoRF binding (P = 0.0527)
MVP		0.66
ClinPred		0.93	D
GERP RS		4.4
Varity_R		0.26
gMVP		0.51
Mutation Taster		=99/1	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: rs139709130; hg19: chr22-37602842; COSMIC: COSV60730714;