22-37206569-G-T

Variant names:

• chr22-37206569-G-T
• rs372352171
• NM_001051.5:c.1235C>A

Variant summary

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

The NM_001051.5(SSTR3):​c.1235C>A​(p.Thr412Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 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. T412M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SSTR3 NM_001051.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285
• Publications: 2 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: 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=0.053004473).

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.1235C>A	p.Thr412Lys	missense	Exon 2 of 2	NP_001042.1	P32745
	SSTR3	NM_001278687.2		c.1235C>A	p.Thr412Lys	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.1235C>A	p.Thr412Lys	missense	Exon 2 of 2	ENSP00000480971.1	P32745
	SSTR3	ENST00000617123.1	TSL:1	c.1235C>A	p.Thr412Lys	missense	Exon 2 of 2	ENSP00000481325.1	P32745
	SSTR3	ENST00000959749.1		c.1235C>A	p.Thr412Lys	missense	Exon 3 of 3	ENSP00000629808.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	1.6
DANN	Benign	0.43
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.28
PrimateAI	Benign	0.26	T
Sift4G	Benign	0.47	T
Polyphen		0.0010	B
Vest4		0.037
MutPred		0.21		Gain of ubiquitination at T412 (P = 0.0048)
MVP		0.24
ClinPred		0.11	T
GERP RS		2.0
Varity_R		0.028
gMVP		0.54
Mutation Taster		=100/0	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: rs372352171; hg19: chr22-37602608;