Genetic Variant CLPTM1:p.Pro309Pro (chr19-44987312-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001294.4(CLPTM1):c.927A>G(p.Pro309Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,614,028 control chromosomes in the GnomAD database, including 95,748 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.39 ( 11929 hom., cov: 35)

Exomes 𝑓: 0.33 ( 83819 hom. )

Consequence

CLPTM1
NM_001294.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.33

Publications

25 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: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP7

Synonymous conserved (PhyloP=-5.33 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CLPTM1	NM_001294.4 link	c.927A>G	p.Pro309Pro	synonymous_variant	Exon 8 of 14	ENST00000337392.10	NP_001285.1
CLPTM1	NM_001282175.2 link	c.885A>G	p.Pro295Pro	synonymous_variant	Exon 8 of 14		NP_001269104.1
CLPTM1	NM_001282176.2 link	c.621A>G	p.Pro207Pro	synonymous_variant	Exon 8 of 14		NP_001269105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLPTM1	ENST00000337392.10 link	c.927A>G	p.Pro309Pro	synonymous_variant	Exon 8 of 14	1	NM_001294.4	ENSP00000336994.4

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58857

AN:

152056

Hom.:

11905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.479

Gnomad AMI

AF:

0.287

Gnomad AMR

AF:

0.409

Gnomad ASJ

AF:

0.364

Gnomad EAS

AF:

0.494

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.387

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.387

GnomAD2 exomes

AF:

0.371

AC:

93177

AN:

251422

AF XY:

0.361

show subpopulations

Gnomad AFR exome

AF:

0.479

Gnomad AMR exome

AF:

0.455

Gnomad ASJ exome

AF:

0.376

Gnomad EAS exome

AF:

0.482

Gnomad FIN exome

AF:

0.386

Gnomad NFE exome

AF:

0.326

Gnomad OTH exome

AF:

0.358

GnomAD4 exome

AF:

0.335

AC:

489197

AN:

1461854

Hom.:

83819

Cov.:

AF XY:

0.333

AC XY:

242378

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.470

AC:

15735

AN:

33480

American (AMR)

AF:

0.450

AC:

20139

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

9766

AN:

26136

East Asian (EAS)

AF:

0.462

AC:

18342

AN:

39700

South Asian (SAS)

AF:

0.314

AC:

27092

AN:

86258

European-Finnish (FIN)

AF:

0.382

AC:

20413

AN:

53408

Middle Eastern (MID)

AF:

0.350

AC:

2019

AN:

5768

European-Non Finnish (NFE)

AF:

0.319

AC:

354321

AN:

1111986

Other (OTH)

AF:

0.354

AC:

21370

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

20617

41234

61850

82467

103084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11722

23444

35166

46888

58610

<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:

0.387

AC:

58934

AN:

152174

Hom.:

11929

Cov.:

AF XY:

0.389

AC XY:

28969

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.479

AC:

19887

AN:

41518

American (AMR)

AF:

0.409

AC:

6256

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.364

AC:

1263

AN:

3468

East Asian (EAS)

AF:

0.495

AC:

2557

AN:

5168

South Asian (SAS)

AF:

0.337

AC:

1628

AN:

4828

European-Finnish (FIN)

AF:

0.387

AC:

4095

AN:

10590

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.325

AC:

22075

AN:

67996

Other (OTH)

AF:

0.389

AC:

823

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1959

3918

5877

7836

9795

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

556

1112

1668

2224

2780

<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:

0.344

Hom.:

8800

Bravo

AF:

0.396

Asia WGS

AF:

0.425

AC:

1479

AN:

3478

EpiCase

AF:

0.328

EpiControl

AF:

0.332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.081

(source)

DANN

Benign

0.48

PhyloP100

-5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over