rs747905422
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_007272.3(CTRC):c.85C>T(p.Arg29Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,611,576 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 Likely pathogenic (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000024 ( 0 hom. )
Consequence
CTRC
NM_007272.3 stop_gained
NM_007272.3 stop_gained
Scores
2
3
2
Clinical Significance
Conservation
PhyloP100: 0.578
Genes affected
CTRC (HGNC:2523): (chymotrypsin C) This gene encodes a member of the peptidase S1 family. The encoded protein is a serum calcium-decreasing factor that has chymotrypsin-like protease activity. Alternatively spliced transcript variants have been observed, but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 22 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-15440344-C-T is Pathogenic according to our data. Variant chr1-15440344-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 576351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CTRC | NM_007272.3 | c.85C>T | p.Arg29Ter | stop_gained | 2/8 | ENST00000375949.5 | |
CTRC | XM_011540550.2 | c.85C>T | p.Arg29Ter | stop_gained | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CTRC | ENST00000375949.5 | c.85C>T | p.Arg29Ter | stop_gained | 2/8 | 1 | NM_007272.3 | P1 | |
CTRC | ENST00000375943.6 | c.40+1840C>T | intron_variant | 1 | |||||
CTRC | ENST00000476813.5 | n.52+1840C>T | intron_variant, non_coding_transcript_variant | 3 | |||||
CTRC | ENST00000483406.1 | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152068Hom.: 0 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
2
AN:
152068
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 246214Hom.: 0 AF XY: 0.0000225 AC XY: 3AN XY: 133448
GnomAD3 exomes
AF:
AC:
3
AN:
246214
Hom.:
AF XY:
AC XY:
3
AN XY:
133448
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000240 AC: 35AN: 1459508Hom.: 0 Cov.: 34 AF XY: 0.0000262 AC XY: 19AN XY: 725850
GnomAD4 exome
AF:
AC:
35
AN:
1459508
Hom.:
Cov.:
34
AF XY:
AC XY:
19
AN XY:
725850
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152068Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74292
GnomAD4 genome
?
AF:
AC:
2
AN:
152068
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
74292
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
?
AF:
AC:
2
Asia WGS
AF:
AC:
2
AN:
3478
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary pancreatitis Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 10, 2018 | This sequence change creates a premature translational stop signal (p.Arg29*) in the CTRC gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with CTRC-related disease. Loss-of-function variants in CTRC are known to be pathogenic (PMID: 22942235). For these reasons, this variant has been classified as Pathogenic. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 26, 2024 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 21, 2020 | The p.R29* variant (also known as c.85C>T), located in coding exon 2 of the CTRC gene, results from a C to T substitution at nucleotide position 85. This changes the amino acid from an arginine to a stop codon within coding exon 2. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 12, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;D
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at