Variant 2-119473469-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002980.3(SCTR):c.389C>T(p.Ser130Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000465 in 1,612,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

SCTR
NM_002980.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.68

Variant links:

Genes affected

SCTR (HGNC:10608): (secretin receptor) The protein encoded by this gene is a G protein-coupled receptor and belongs to the glucagon-VIP-secretin receptor family. It binds secretin which is the most potent regulator of pancreatic bicarbonate, electrolyte and volume secretion. Secretin and its receptor are suggested to be involved in pancreatic cancer and autism. [provided by RefSeq, Jul 2008]

SCTR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22454259).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCTR	NM_002980.3 linkuse as main transcript	c.389C>T	p.Ser130Phe	missense_variant	4/13	ENST00000019103.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SCTR	ENST00000019103.8 linkuse as main transcript	c.389C>T	p.Ser130Phe	missense_variant	4/13	1	NM_002980.3	P1
SCTR	ENST00000627145.1 linkuse as main transcript	c.464C>T	p.Ser155Phe	missense_variant	5/8	5
SCTR	ENST00000630739.2 linkuse as main transcript	c.185C>T	p.Ser62Phe	missense_variant	5/8	5
SCTR	ENST00000485440.1 linkuse as main transcript	n.1167C>T		non_coding_transcript_exon_variant	2/10	2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251364

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135854

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000466

AC:

AN:

1460330

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

726596

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000585

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Mar 01, 2023

The c.389C>T (p.S130F) alteration is located in exon 4 (coding exon 4) of the SCTR gene. This alteration results from a C to T substitution at nucleotide position 389, causing the serine (S) at amino acid position 130 to be replaced by a phenylalanine (F). 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

0.15

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.45

T;.;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.9

D;.;.

REVEL

Benign

0.16

Sift

Uncertain

0.027

D;.;.

Sift4G

Uncertain

0.047

D;T;D

Polyphen

0.38

B;.;.

Vest4

0.36

MVP

0.66

MPC

0.24

ClinPred

0.30

GERP RS

3.9

Varity_R

0.12

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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