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GeneBe

rs200649005

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_030782.5(CLPTM1L):c.220G>C(p.Val74Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CLPTM1L
NM_030782.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.78
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26834762).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CLPTM1LNM_030782.5 linkuse as main transcriptc.220G>C p.Val74Leu missense_variant 2/17 ENST00000320895.10
CLPTM1LXM_011514144.3 linkuse as main transcriptc.220G>C p.Val74Leu missense_variant 2/17

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CLPTM1LENST00000320895.10 linkuse as main transcriptc.220G>C p.Val74Leu missense_variant 2/171 NM_030782.5 P1Q96KA5-1
CLPTM1LENST00000630539.1 linkuse as main transcriptc.-180G>C 5_prime_UTR_variant 2/165

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461550
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727032
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

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 submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Large deletion encompassing this gene and 4 others has been reported in patient with Cleft lip and palate, syndromic & neuro-psychomotor developmental delay. Impact of missense variant in the gene is unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
Cadd
Benign
17
Dann
Benign
0.76
DEOGEN2
Benign
0.045
T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.85
T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.27
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.89
L
MutationTaster
Benign
0.96
D;D
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.089
Sift
Benign
0.45
T
Sift4G
Benign
0.33
T
Polyphen
0.0020
B
Vest4
0.48
MutPred
0.55
Loss of sheet (P = 0.0025);
MVP
0.50
MPC
0.34
ClinPred
0.54
D
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.076
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs200649005; hg19: chr5-1344509; API