Variant 5-1325759-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_030782.5(CLPTM1L):c.1138G>A(p.Glu380Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00066 in 1,613,284 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00081 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00064 ( 3 hom. )

Consequence

CLPTM1L
NM_030782.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.146

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004665613).

BP6

Variant 5-1325759-C-T is Benign according to our data. Variant chr5-1325759-C-T is described in ClinVar as [Benign]. Clinvar id is 3052632.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CLPTM1L	NM_030782.5 linkuse as main transcript	c.1138G>A	p.Glu380Lys	missense_variant	10/17	ENST00000320895.10
CLPTM1L	XM_011514144.3 linkuse as main transcript	c.1135G>A	p.Glu379Lys	missense_variant	10/17
CLPTM1L	XM_024446222.2 linkuse as main transcript	c.604G>A	p.Glu202Lys	missense_variant	8/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLPTM1L	ENST00000320895.10 linkuse as main transcript	c.1138G>A	p.Glu380Lys	missense_variant	10/17	1	NM_030782.5	P1	Q96KA5-1

Frequencies

GnomAD3 genomes

AF:

0.000808

AC:

123

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00981

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000558

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000911

AC:

229

AN:

251344

Hom.:

AF XY:

0.000913

AC XY:

124

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.0110

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000589

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.000645

AC:

942

AN:

1460970

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

468

AN XY:

726816

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.0107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000460

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.000808

AC:

123

AN:

152314

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00981

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.000771

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000807

AC:

EpiCase

AF:

0.000927

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CLPTM1L-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 15, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.65

Cadd

Benign

0.35

Dann

Benign

0.36

DEOGEN2

Benign

0.018

T;.;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.28

T;.;T

M_CAP

Benign

0.0091

MetaRNN

Benign

0.0047

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.39

N;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

0.63

N;N;.

REVEL

Benign

0.027

Sift

Benign

0.84

T;T;.

Sift4G

Benign

0.73

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.18

MVP

0.20

MPC

0.37

ClinPred

0.00071

GERP RS

-1.9

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.1

Varity_R

0.022

gMVP

0.38

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