Variant 5-1323805-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_030782.5(CLPTM1L):c.1262T>C(p.Leu421Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000639 in 1,613,148 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 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

CLPTM1L
NM_030782.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.72

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]

CLPTM1L links:

Genome browser will be placed here

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, 0.889

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CLPTM1L	NM_030782.5 linkuse as main transcript	c.1262T>C	p.Leu421Pro	missense_variant	12/17	ENST00000320895.10	NP_110409.2
CLPTM1L	XM_011514144.3 linkuse as main transcript	c.1259T>C	p.Leu420Pro	missense_variant	12/17		XP_011512446.1
CLPTM1L	XM_024446222.2 linkuse as main transcript	c.728T>C	p.Leu243Pro	missense_variant	10/15		XP_024301990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLPTM1L	ENST00000320895.10 linkuse as main transcript	c.1262T>C	p.Leu421Pro	missense_variant	12/17	1	NM_030782.5	ENSP00000313854	P1	Q96KA5-1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000637

AC:

AN:

251310

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000925

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000643

AC:

AN:

1460926

Hom.:

Cov.:

AF XY:

0.0000633

AC XY:

AN XY:

726850

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:

0.0000752

Gnomad4 NFE exome

AF:

0.0000765

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000724

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Mar 20, 2023

The c.1262T>C (p.L421P) alteration is located in exon 12 (coding exon 12) of the CLPTM1L gene. This alteration results from a T to C substitution at nucleotide position 1262, causing the leucine (L) at amino acid position 421 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Uncertain

0.091

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

T;.;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

D;.;D

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.89

D;D;D

MetaSVM

Benign

-0.50

MutationAssessor

Pathogenic

2.9

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-4.6

D;D;.

REVEL

Uncertain

0.51

Sift

Uncertain

0.0010

D;D;.

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.93

MVP

0.37

MPC

1.3

ClinPred

0.83

GERP RS

4.5

Varity_R

0.85

gMVP

0.88

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over