chr5-1331869-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_030782.5(CLPTM1L):c.906C>G(p.Phe302Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,244 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 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
CLPTM1L
NM_030782.5 missense
NM_030782.5 missense
Scores
4
9
6
Clinical Significance
Conservation
PhyloP100: 2.37
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, 0.866
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CLPTM1L | NM_030782.5 | c.906C>G | p.Phe302Leu | missense_variant | 8/17 | ENST00000320895.10 | |
CLPTM1L | XM_011514144.3 | c.903C>G | p.Phe301Leu | missense_variant | 8/17 | ||
CLPTM1L | XM_024446222.2 | c.372C>G | p.Phe124Leu | missense_variant | 6/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CLPTM1L | ENST00000320895.10 | c.906C>G | p.Phe302Leu | missense_variant | 8/17 | 1 | NM_030782.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152224Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250142Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135690
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461020Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 726800
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74372
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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 | Jan 31, 2024 | The c.906C>G (p.F302L) alteration is located in exon 8 (coding exon 8) of the CLPTM1L gene. This alteration results from a C to G substitution at nucleotide position 906, causing the phenylalanine (F) at amino acid position 302 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
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;.
REVEL
Benign
Sift
Uncertain
D;D;.
Sift4G
Benign
T;T;T
Polyphen
D;D;D
Vest4
MutPred
Gain of ubiquitination at K306 (P = 0.123);.;.;
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