2-119464247-T-A
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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):c.512A>T(p.His171Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,040 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 (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
SCTR
NM_002980.3 missense
NM_002980.3 missense
Scores
3
9
7
Clinical Significance
Conservation
PhyloP100: 2.08
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, 0.748
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCTR | NM_002980.3 | c.512A>T | p.His171Leu | missense_variant | 6/13 | ENST00000019103.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCTR | ENST00000019103.8 | c.512A>T | p.His171Leu | missense_variant | 6/13 | 1 | NM_002980.3 | P1 | |
SCTR | ENST00000627145.1 | c.587A>T | p.His196Leu | missense_variant | 7/8 | 5 | |||
SCTR | ENST00000630739.2 | c.308A>T | p.His103Leu | missense_variant | 7/8 | 5 | |||
SCTR | ENST00000485440.1 | n.1192A>T | non_coding_transcript_exon_variant | 3/10 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152056Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251096Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135724
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GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461866Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727232
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74406
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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 | May 04, 2023 | The c.512A>T (p.H171L) alteration is located in exon 6 (coding exon 6) of the SCTR gene. This alteration results from a A to T substitution at nucleotide position 512, causing the histidine (H) at amino acid position 171 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Uncertain
T;.;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;.
REVEL
Benign
Sift
Uncertain
D;.;.
Sift4G
Uncertain
D;D;D
Polyphen
B;.;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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