Variant 5-1331803-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_030782.5(CLPTM1L):c.972G>T(p.Lys324Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CLPTM1L
NM_030782.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.914

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:

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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=0.39826402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CLPTM1L	NM_030782.5 linkuse as main transcript	c.972G>T	p.Lys324Asn	missense_variant	8/17	ENST00000320895.10	NP_110409.2
CLPTM1L	XM_011514144.3 linkuse as main transcript	c.969G>T	p.Lys323Asn	missense_variant	8/17		XP_011512446.1
CLPTM1L	XM_024446222.2 linkuse as main transcript	c.438G>T	p.Lys146Asn	missense_variant	6/15		XP_024301990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLPTM1L	ENST00000320895.10 linkuse as main transcript	c.972G>T	p.Lys324Asn	missense_variant	8/17	1	NM_030782.5	ENSP00000313854	P1	Q96KA5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

250360

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460942

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726768

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000284

Hom.:

ExAC

AF:

0.0000247

AC:

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

Oct 10, 2023

The c.972G>T (p.K324N) alteration is located in exon 8 (coding exon 8) of the CLPTM1L gene. This alteration results from a G to T substitution at nucleotide position 972, causing the lysine (K) at amino acid position 324 to be replaced by an asparagine (N). 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

0.92

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.95

D;.;D

M_CAP

Benign

0.046

MetaRNN

Benign

0.37

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.9

M;.;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-2.2

N;N;.

REVEL

Benign

0.088

Sift

Benign

0.032

D;D;.

Sift4G

Benign

0.068

T;D;D

Polyphen

0.0040

B;B;B

Vest4

0.75

MutPred

0.69

Loss of ubiquitination at K324 (P = 0.0412);.;.;

MVP

0.29

MPC

0.41

ClinPred

0.36

GERP RS

-0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.74

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