rs193920801
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_030782.5(CLPTM1L):c.749G>A(p.Arg250His) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,528 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 (no stars).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
CLPTM1L
NM_030782.5 missense
NM_030782.5 missense
Scores
3
11
5
Clinical Significance
Conservation
PhyloP100: 5.42
Genes affected
CLPTM1L (HGNC:24308): (CLPTM1 like) The protein encoded by this gene is a membrane protein whose overexpression in cisplatin-sensitive cells causes apoptosis. Polymorphisms in this gene have been reported to increase susceptibility to several cancers, including lung, pancreatic, and breast cancers. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.861
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLPTM1L | NM_030782.5 | c.749G>A | p.Arg250His | missense_variant | 6/17 | ENST00000320895.10 | |
CLPTM1L | XM_011514144.3 | c.746G>A | p.Arg249His | missense_variant | 6/17 | ||
CLPTM1L | XM_024446222.2 | c.215G>A | p.Arg72His | missense_variant | 4/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLPTM1L | ENST00000320895.10 | c.749G>A | p.Arg250His | missense_variant | 6/17 | 1 | NM_030782.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152256Hom.: 0 Cov.: 34
GnomAD3 genomes
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461272Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726936
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152256Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74382
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Malignant tumor of prostate Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | Science for Life laboratory, Karolinska Institutet | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.
REVEL
Benign
Sift
Uncertain
D;D;.
Sift4G
Uncertain
D;D;D
Polyphen
D;D;D
Vest4
MutPred
Loss of methylation at R250 (P = 0.0183);.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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