Variant 3-187669234-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001048.4(SST):c.182A>C(p.Asn61Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,613,872 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0089 ( 11 hom., cov: 32)

Exomes 𝑓: 0.012 ( 133 hom. )

Consequence

SST
NM_001048.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.40

Variant links:

Genes affected

SST (HGNC:11329): (somatostatin) The hormone somatostatin has active 14 aa and 28 aa forms that are produced by alternate cleavage of the single preproprotein encoded by this gene. Somatostatin is expressed throughout the body and inhibits the release of numerous secondary hormones by binding to high-affinity G-protein-coupled somatostatin receptors. This hormone is an important regulator of the endocrine system through its interactions with pituitary growth hormone, thyroid stimulating hormone, and most hormones of the gastrointestinal tract. Somatostatin also affects rates of neurotransmission in the central nervous system and proliferation of both normal and tumorigenic cells. [provided by RefSeq, Jul 2008]

SST links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048260093).

BP6

Variant 3-187669234-T-G is Benign according to our data. Variant chr3-187669234-T-G is described in ClinVar as [Benign]. Clinvar id is 791576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1356 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SST	NM_001048.4 linkuse as main transcript	c.182A>C	p.Asn61Thr	missense_variant	2/2	ENST00000287641.4	NP_001039.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SST	ENST00000287641.4 linkuse as main transcript	c.182A>C	p.Asn61Thr	missense_variant	2/2	1	NM_001048.4	ENSP00000287641	P1

Frequencies

GnomAD3 genomes

AF:

0.00893

AC:

1357

AN:

151926

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00300

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00832

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00482

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0140

Gnomad OTH

AF:

0.00722

GnomAD3 exomes

AF:

0.00867

AC:

2180

AN:

251456

Hom.:

AF XY:

0.00840

AC XY:

1142

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00234

Gnomad AMR exome

AF:

0.00555

Gnomad ASJ exome

AF:

0.0228

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00408

Gnomad FIN exome

AF:

0.00342

Gnomad NFE exome

AF:

0.0127

Gnomad OTH exome

AF:

0.0132

GnomAD4 exome

AF:

0.0123

AC:

17966

AN:

1461828

Hom.:

133

Cov.:

AF XY:

0.0120

AC XY:

8732

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00209

Gnomad4 AMR exome

AF:

0.00557

Gnomad4 ASJ exome

AF:

0.0215

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00322

Gnomad4 FIN exome

AF:

0.00412

Gnomad4 NFE exome

AF:

0.0143

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.00892

AC:

1356

AN:

152044

Hom.:

Cov.:

AF XY:

0.00851

AC XY:

633

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00299

Gnomad4 AMR

AF:

0.00831

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00291

Gnomad4 FIN

AF:

0.00482

Gnomad4 NFE

AF:

0.0140

Gnomad4 OTH

AF:

0.00714

Alfa

AF:

0.0121

Hom.:

Bravo

AF:

0.00849

TwinsUK

AF:

0.0183

AC:

ALSPAC

AF:

0.0143

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0134

AC:

115

ExAC

AF:

0.00841

AC:

1021

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0140

EpiControl

AF:

0.0132

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 22, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.15

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.085

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0048

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

MutationTaster

Benign

0.77

PrimateAI

Benign

0.39

PROVEAN

Benign

0.30

REVEL

Benign

0.15

Sift

Benign

0.42

Sift4G

Benign

0.59

Polyphen

0.0

Vest4

0.25

MVP

0.068

MPC

0.35

ClinPred

0.016

GERP RS

4.4

Varity_R

0.054

gMVP

0.058

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