11-626788-C-T

Variant summary

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

The NM_021920.4(SCT):​c.175G>A​(p.Glu59Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000323 in 1,549,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

SCT
NM_021920.4 missense, splice_region

Scores

1
3
14
Splicing: ADA: 0.09325
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.292
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11687958).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SCTNM_021920.4 linkuse as main transcriptc.175G>A p.Glu59Lys missense_variant, splice_region_variant 3/4 ENST00000176195.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SCTENST00000176195.4 linkuse as main transcriptc.175G>A p.Glu59Lys missense_variant, splice_region_variant 3/41 NM_021920.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152116
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000675
AC:
1
AN:
148068
Hom.:
0
AF XY:
0.0000127
AC XY:
1
AN XY:
78442
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:
0.0000186
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000344
AC:
48
AN:
1397112
Hom.:
0
Cov.:
32
AF XY:
0.0000334
AC XY:
23
AN XY:
688932
show subpopulations
Gnomad4 AFR exome
AF:
0.0000317
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:
0.0000408
Gnomad4 OTH exome
AF:
0.0000518
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152116
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000387
Hom.:
0
Bravo
AF:
0.0000113

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 GeneticsSep 17, 2021The c.175G>A (p.E59K) alteration is located in exon 3 (coding exon 3) of the SCT gene. This alteration results from a G to A substitution at nucleotide position 175, causing the glutamic acid (E) at amino acid position 59 to be replaced by a lysine (K). 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
0.23
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.56
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.45
FATHMM_MKL
Benign
0.74
D
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
0.93
N
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-0.76
N
REVEL
Benign
0.024
Sift
Uncertain
0.017
D
Sift4G
Uncertain
0.034
D
Polyphen
0.72
P
Vest4
0.26
MVP
0.51
MPC
0.68
ClinPred
0.50
D
GERP RS
1.3
Varity_R
0.16
gMVP
0.12

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.093
dbscSNV1_RF
Benign
0.14
SpliceAI score (max)
0.29
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.29
Position offset: -3

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: rs1344087084; hg19: chr11-626788; API