Genetic Variant CLPTM1:p.Ala2Val (chr19-44955400-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001294.4(CLPTM1):c.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000478 in 1,318,350 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 (★). Synonymous variant affecting the same amino acid position (i.e. A2A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

CLPTM1
NM_001294.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.82

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20927477).

BS2

High AC in GnomAd4 at 20 AD gene.

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.5C>T	p.Ala2Val	missense	Exon 1 of 14	NP_001285.1	A0A0S2Z3H2
CLPTM1	NM_001282175.2		c.30+315C>T		intron	N/A	NP_001269104.1	O96005-4
CLPTM1	NM_001282176.2		c.-235+699C>T		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.5C>T	p.Ala2Val	missense	Exon 1 of 14	ENSP00000336994.4	O96005-1
CLPTM1	ENST00000588855.5	TSL:1	n.117+699C>T		intron	N/A
CLPTM1	ENST00000870268.1		c.5C>T	p.Ala2Val	missense	Exon 1 of 15	ENSP00000540327.1

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

151814

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000333

AC:

AN:

12024

AF XY:

0.000154

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000618

Gnomad OTH exome

AF:

0.00287

GnomAD4 exome

AF:

0.0000369

AC:

AN:

1166536

Hom.:

Cov.:

AF XY:

0.0000392

AC XY:

AN XY:

561740

show subpopulations

African (AFR)

AF:

0.0000433

AC:

AN:

23096

American (AMR)

AF:

0.000668

AC:

AN:

10476

Ashkenazi Jewish (ASJ)

AF:

0.000637

AC:

AN:

15706

East Asian (EAS)

AF:

0.00

AC:

AN:

28300

South Asian (SAS)

AF:

0.00

AC:

AN:

41010

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3190

European-Non Finnish (NFE)

AF:

0.0000135

AC:

AN:

964842

Other (OTH)

AF:

0.000252

AC:

AN:

47644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

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

AF:

0.000132

AC:

AN:

151814

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74132

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41302

American (AMR)

AF:

0.00105

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10526

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67966

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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:

0.00

Hom.:

Bravo

AF:

0.000287

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.026

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.67

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.55

PhyloP100

2.8

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

0.020

REVEL

Benign

0.073

Sift

Benign

0.28

Sift4G

Uncertain

0.060

Polyphen

1.0

Vest4

0.45

MutPred

0.31

Gain of stability (P = 0.0174)

MVP

0.38

MPC

1.5

ClinPred

0.32

GERP RS

3.4

PromoterAI

-0.44

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.15

gMVP

0.67

Mutation Taster

=85/15

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over