Genetic Variant CLPTM1:p.Gly9Glu (chr19-44955421-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001294.4(CLPTM1):c.26G>A(p.Gly9Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000844 in 1,184,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 8.4e-7 ( 0 hom. )

Consequence

CLPTM1
NM_001294.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.56

Publications

3 publications found

Variant links:

Genes affected

CLPTM1 (HGNC:2087): (CLPTM1 regulator of GABA type A receptor forward trafficking) Predicted to be involved in regulation of T cell differentiation in thymus. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

CLPTM1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2114265).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001294.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLPTM1	NM_001294.4	MANE Select	c.26G>A	p.Gly9Glu	missense	Exon 1 of 14	NP_001285.1	A0A0S2Z3H2
CLPTM1	NM_001282175.2		c.30+336G>A		intron	N/A	NP_001269104.1	O96005-4
CLPTM1	NM_001282176.2		c.-235+720G>A		intron	N/A	NP_001269105.1	O96005-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLPTM1	ENST00000337392.10	TSL:1 MANE Select	c.26G>A	p.Gly9Glu	missense	Exon 1 of 14	ENSP00000336994.4	O96005-1
CLPTM1	ENST00000588855.5	TSL:1	n.117+720G>A		intron	N/A
CLPTM1	ENST00000870268.1		c.26G>A	p.Gly9Glu	missense	Exon 1 of 15	ENSP00000540327.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.44e-7

AC:

AN:

1184564

Hom.:

Cov.:

AF XY:

0.00000175

AC XY:

AN XY:

570554

show subpopulations

African (AFR)

AF:

0.0000432

AC:

AN:

23148

American (AMR)

AF:

0.00

AC:

AN:

10674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16002

East Asian (EAS)

AF:

0.00

AC:

AN:

28438

South Asian (SAS)

AF:

0.00

AC:

AN:

42980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36092

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3254

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

975454

Other (OTH)

AF:

0.00

AC:

AN:

48522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

Eigen

Benign

0.12

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.60

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

3.6

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.41

REVEL

Benign

0.15

Sift

Benign

0.33

Sift4G

Benign

0.42

Polyphen

1.0

Vest4

0.45

MutPred

0.22

Gain of helix (P = 0.0022)

MVP

0.41

MPC

2.0

ClinPred

0.77

GERP RS

3.4

PromoterAI

0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.66

Mutation Taster

=81/19

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over