Variant chr20-23035622-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001052.4(SSTR4):c.139A>G(p.Met47Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000115 in 1,544,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

SSTR4
NM_001052.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.22

Variant links:

Genes affected

SSTR4 (HGNC:11333): (somatostatin receptor 4) Somatostatin acts at many sites to inhibit the release of many hormones and other secretory proteins. The biologic effects of somatostatin are probably mediated by a family of G protein-coupled receptors that are expressed in a tissue-specific manner. SSTR4 is a member of the superfamily of receptors having seven transmembrane segments and is expressed in highest levels in fetal and adult brain and lung. [provided by RefSeq, Jul 2008]

SSTR4 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050096333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SSTR4	NM_001052.4 linkuse as main transcript	c.139A>G	p.Met47Val	missense_variant	1/1	ENST00000255008.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SSTR4	ENST00000255008.5 linkuse as main transcript	c.139A>G	p.Met47Val	missense_variant	1/1		NM_001052.4	P1
	ENST00000440921.6 linkuse as main transcript	n.827-2601A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000790

AC:

AN:

151922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000393

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000928

AC:

AN:

183242

Hom.:

AF XY:

0.0000712

AC XY:

AN XY:

98270

show subpopulations

Gnomad AFR exome

AF:

0.0000739

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000486

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000103

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000119

AC:

166

AN:

1392302

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

687586

show subpopulations

Gnomad4 AFR exome

AF:

0.0000329

Gnomad4 AMR exome

AF:

0.0000297

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000185

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000139

Gnomad4 OTH exome

AF:

0.0000873

GnomAD4 genome

AF:

0.0000790

AC:

AN:

151922

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000393

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000907

ExAC

AF:

0.0000748

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.139A>G (p.M47V) alteration is located in exon 1 (coding exon 1) of the SSTR4 gene. This alteration results from a A to G substitution at nucleotide position 139, causing the methionine (M) at amino acid position 47 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.017

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.47

M_CAP

Benign

0.0074

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.78

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.27

REVEL

Benign

0.039

Sift

Benign

0.40

Sift4G

Benign

1.0

Polyphen

0.013

Vest4

0.21

MVP

0.27

MPC

0.44

ClinPred

0.014

GERP RS

2.4

Varity_R

0.19

gMVP

0.37

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over