11-626736-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021920.4(SCT):ā€‹c.227T>Gā€‹(p.Leu76Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000452 in 1,550,288 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000043 ( 0 hom. )

Consequence

SCT
NM_021920.4 missense

Scores

1
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.426
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCTNM_021920.4 linkuse as main transcriptc.227T>G p.Leu76Arg missense_variant 3/4 ENST00000176195.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCTENST00000176195.4 linkuse as main transcriptc.227T>G p.Leu76Arg missense_variant 3/41 NM_021920.4 P1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151996
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000194
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000265
AC:
4
AN:
150872
Hom.:
0
AF XY:
0.0000375
AC XY:
3
AN XY:
79902
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000271
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000179
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000429
AC:
6
AN:
1398292
Hom.:
0
Cov.:
32
AF XY:
0.00000580
AC XY:
4
AN XY:
689680
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000560
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000371
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151996
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74238
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

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 submitterclinical testingAmbry GeneticsOct 27, 2022The c.227T>G (p.L76R) alteration is located in exon 3 (coding exon 3) of the SCT gene. This alteration results from a T to G substitution at nucleotide position 227, causing the leucine (L) at amino acid position 76 to be replaced by an arginine (R). 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
0.12
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.11
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.23
T
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.31
FATHMM_MKL
Benign
0.52
D
M_CAP
Uncertain
0.090
D
MetaRNN
Uncertain
0.74
D
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.55
T
PROVEAN
Uncertain
-2.5
D
REVEL
Uncertain
0.32
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0030
D
Polyphen
0.95
P
Vest4
0.81
MutPred
0.49
Gain of MoRF binding (P = 0.0147);
MVP
0.74
MPC
1.0
ClinPred
0.17
T
GERP RS
2.8
Varity_R
0.45
gMVP
0.22

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs1195011573; hg19: chr11-626736; API