Variant 5-1325767-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_030782.5(CLPTM1L):c.1130T>C(p.Leu377Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000471 in 1,613,750 control chromosomes in the GnomAD database, including 1 homozygotes. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

CLPTM1L
NM_030782.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CLPTM1L	NM_030782.5 linkuse as main transcript	c.1130T>C	p.Leu377Pro	missense_variant	10/17	ENST00000320895.10	NP_110409.2
CLPTM1L	XM_011514144.3 linkuse as main transcript	c.1127T>C	p.Leu376Pro	missense_variant	10/17		XP_011512446.1
CLPTM1L	XM_024446222.2 linkuse as main transcript	c.596T>C	p.Leu199Pro	missense_variant	8/15		XP_024301990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLPTM1L	ENST00000320895.10 linkuse as main transcript	c.1130T>C	p.Leu377Pro	missense_variant	10/17	1	NM_030782.5	ENSP00000313854	P1	Q96KA5-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000597

AC:

AN:

251386

Hom.:

AF XY:

0.0000810

AC XY:

AN XY:

135872

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:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000465

AC:

AN:

1461402

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

727010

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000567

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000975

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000296

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 31, 2024

The c.1130T>C (p.L377P) alteration is located in exon 10 (coding exon 10) of the CLPTM1L gene. This alteration results from a T to C substitution at nucleotide position 1130, causing the leucine (L) at amino acid position 377 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

Benign

0.098

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.054

T;.;.

Eigen

Benign

-0.057

Eigen_PC

Benign

-0.062

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.80

T;.;T

M_CAP

Benign

0.041

MetaRNN

Uncertain

0.72

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.2

N;N;.

REVEL

Benign

0.21

Sift

Benign

0.20

T;T;.

Sift4G

Benign

0.20

T;T;T

Polyphen

0.88

P;P;P

Vest4

0.62

MutPred

0.65

Gain of disorder (P = 0.0376);.;.;

MVP

0.30

MPC

0.55

ClinPred

0.22

GERP RS

4.3

Varity_R

0.22

gMVP

0.70

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