Genetic Variant CLPTM1:p.Val14Met (chr19-44955435-G-A) – 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.40G>A(p.Val14Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 1,333,880 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: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

CLPTM1
NM_001294.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.56

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:

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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=0.26179323).

BS2

High AC in GnomAdExome4 at 28 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.40G>A	p.Val14Met	missense	Exon 1 of 14	NP_001285.1	A0A0S2Z3H2
CLPTM1	NM_001282175.2		c.30+350G>A		intron	N/A	NP_001269104.1	O96005-4
CLPTM1	NM_001282176.2		c.-235+734G>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.40G>A	p.Val14Met	missense	Exon 1 of 14	ENSP00000336994.4	O96005-1
CLPTM1	ENST00000588855.5	TSL:1	n.117+734G>A		intron	N/A
CLPTM1	ENST00000870268.1		c.40G>A	p.Val14Met	missense	Exon 1 of 15	ENSP00000540327.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

12930

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000237

AC:

AN:

1181650

Hom.:

Cov.:

AF XY:

0.0000247

AC XY:

AN XY:

567394

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23280

American (AMR)

AF:

0.00

AC:

AN:

10178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15896

East Asian (EAS)

AF:

0.00

AC:

AN:

28150

South Asian (SAS)

AF:

0.00

AC:

AN:

39306

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3290

European-Non Finnish (NFE)

AF:

0.0000276

AC:

AN:

976824

Other (OTH)

AF:

0.0000207

AC:

AN:

48334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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:

0.0000197

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41472

American (AMR)

AF:

0.000131

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

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

Benign

0.30

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

Eigen

Benign

0.12

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.69

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

3.6

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.15

REVEL

Uncertain

0.29

Sift

Benign

0.040

Sift4G

Benign

0.27

Polyphen

0.94

Vest4

0.26

MutPred

0.19

Loss of sheet (P = 0.0025)

MVP

0.28

MPC

1.7

ClinPred

0.89

GERP RS

3.4

PromoterAI

0.30

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.28

Mutation Taster

=88/12

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