2-119446866-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_002980.3(SCTR):āc.1033C>Gā(p.Leu345Val) variant causes a missense change. The variant allele was found at a frequency of 0.000127 in 1,561,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00013 ( 0 hom., cov: 32)
Exomes š: 0.00013 ( 0 hom. )
Consequence
SCTR
NM_002980.3 missense
NM_002980.3 missense
Scores
4
10
5
Clinical Significance
Conservation
PhyloP100: 5.55
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.829
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCTR | NM_002980.3 | c.1033C>G | p.Leu345Val | missense_variant | 11/13 | ENST00000019103.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCTR | ENST00000019103.8 | c.1033C>G | p.Leu345Val | missense_variant | 11/13 | 1 | NM_002980.3 | P1 | |
SCTR | ENST00000485440.1 | n.1713C>G | non_coding_transcript_exon_variant | 8/10 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152204Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000122 AC: 27AN: 221126Hom.: 0 AF XY: 0.000125 AC XY: 15AN XY: 119988
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GnomAD4 exome AF: 0.000127 AC: 179AN: 1409482Hom.: 0 Cov.: 30 AF XY: 0.000136 AC XY: 95AN XY: 700296
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GnomAD4 genome ? AF: 0.000131 AC: 20AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74364
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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 | Sep 06, 2022 | The c.1033C>G (p.L345V) alteration is located in exon 11 (coding exon 11) of the SCTR gene. This alteration results from a C to G substitution at nucleotide position 1033, causing the leucine (L) at amino acid position 345 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at