dbSNP rs150678949: CLPTM1L:p.Glu380Lys (chr5-1325759-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

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 no assertion criteria provided B:1

Conservation

PhyloP100: -0.146

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -9 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 VariationId is 3052632.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030782.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLPTM1L	NM_030782.5	MANE Select	c.1138G>A	p.Glu380Lys	missense	Exon 10 of 17	NP_110409.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLPTM1L	ENST00000320895.10	TSL:1 MANE Select	c.1138G>A	p.Glu380Lys	missense	Exon 10 of 17	ENSP00000313854.5	Q96KA5-1
CLPTM1L	ENST00000507807.3	TSL:1	c.631G>A	p.Glu211Lys	missense	Exon 7 of 14	ENSP00000423321.1	G5E9Z2
CLPTM1L	ENST00000966757.1		c.1138G>A	p.Glu380Lys	missense	Exon 10 of 18	ENSP00000636816.1

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

GnomAD2 exomes

AF:

0.000911

AC:

229

AN:

251344

AF XY:

0.000913

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 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

African (AFR)

AF:

0.00123

AC:

AN:

33458

American (AMR)

AF:

0.000157

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.0107

AC:

280

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.000290

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000460

AC:

511

AN:

1111280

Other (OTH)

AF:

0.00114

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

136

181

226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000808

AC:

123

AN:

152314

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

41562

American (AMR)

AF:

0.000196

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00981

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000559

AC:

AN:

68032

Other (OTH)

AF:

0.000946

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000962

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

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

CLPTM1L-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.35

(source)

DANN

Benign

0.36

DEOGEN2

Benign

0.018

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.28

M_CAP

Benign

0.0091

MetaRNN

Benign

0.0047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.39

PhyloP100

-0.15

PrimateAI

Benign

0.25

PROVEAN

Benign

0.63

REVEL

Benign

0.027

Sift

Benign

0.84

Sift4G

Benign

0.73

Polyphen

0.0

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

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

1.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over