11-626517-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_021920.4(SCT):​c.280G>A​(p.Gly94Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000628 in 1,559,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

SCT
NM_021920.4 missense

Scores

18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.407
Variant links:
Genes affected
SCT (HGNC:10607): (secretin) This gene encodes a member of the glucagon family of peptides. The encoded preproprotein is secreted by endocrine S cells in the proximal small intestinal mucosa as a prohormone, then proteolytically processed to generate the mature peptide hormone. The release of this active peptide hormone is stimulated by either fatty acids or acidic pH in the duodenum. This hormone stimulates the secretion of bile and bicarbonate in the duodenum, pancreatic and biliary ducts. [provided by RefSeq, Feb 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.019119918).
BP6
Variant 11-626517-C-T is Benign according to our data. Variant chr11-626517-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2361956.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCTNM_021920.4 linkuse as main transcriptc.280G>A p.Gly94Arg missense_variant 4/4 ENST00000176195.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCTENST00000176195.4 linkuse as main transcriptc.280G>A p.Gly94Arg missense_variant 4/41 NM_021920.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152190
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000480
AC:
8
AN:
166658
Hom.:
0
AF XY:
0.0000794
AC XY:
7
AN XY:
88126
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:
0.000215
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000302
Gnomad OTH exome
AF:
0.000217
GnomAD4 exome
AF:
0.0000633
AC:
89
AN:
1407108
Hom.:
0
Cov.:
32
AF XY:
0.0000748
AC XY:
52
AN XY:
694738
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000274
Gnomad4 SAS exome
AF:
0.000339
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000508
Gnomad4 OTH exome
AF:
0.0000857
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152308
Hom.:
0
Cov.:
32
AF XY:
0.0000940
AC XY:
7
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.000144
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000264
AC:
3

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsOct 27, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
1.3
DANN
Benign
0.49
DEOGEN2
Benign
0.067
T
Eigen
Benign
-1.9
Eigen_PC
Benign
-2.0
FATHMM_MKL
Benign
0.014
N
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.019
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.55
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.34
T
PROVEAN
Benign
0.43
N
REVEL
Benign
0.013
Sift
Benign
0.16
T
Sift4G
Benign
0.85
T
Polyphen
0.0010
B
Vest4
0.12
MutPred
0.22
Gain of solvent accessibility (P = 0.0037);
MVP
0.11
MPC
0.30
ClinPred
0.027
T
GERP RS
-4.4
Varity_R
0.059
gMVP
0.054

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs536940291; hg19: chr11-626517; COSMIC: COSV51564578; COSMIC: COSV51564578; API