Variant 19-44955401-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_001294.4(CLPTM1):c.6G>A(p.Ala2Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000522 in 1,340,912 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00055 ( 0 hom. )

Consequence

CLPTM1
NM_001294.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.56

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:

CLPTM1 (HGNC:):

CLPTM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 19-44955401-G-A is Benign according to our data. Variant chr19-44955401-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3048348.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=3.57 with no splicing effect.

BS2

High AC in GnomAd4 at 49 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLPTM1	NM_001294.4 linkuse as main transcript	c.6G>A	p.Ala2Ala	synonymous_variant	1/14	ENST00000337392.10	NP_001285.1	O96005-1A0A0S2Z3H2
CLPTM1	NM_001282175.2 linkuse as main transcript	c.30+316G>A		intron_variant			NP_001269104.1	O96005-4
CLPTM1	NM_001282176.2 linkuse as main transcript	c.-235+700G>A		intron_variant			NP_001269105.1	O96005-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLPTM1	ENST00000337392.10 linkuse as main transcript	c.6G>A	p.Ala2Ala	synonymous_variant	1/14	1	NM_001294.4	ENSP00000336994.4		O96005-1

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000691

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000428

AC:

AN:

14022

Hom.:

AF XY:

0.000398

AC XY:

AN XY:

7534

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 SAS exome

AF:

0.00107

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000696

Gnomad OTH exome

AF:

0.00237

GnomAD4 exome

AF:

0.000548

AC:

651

AN:

1188704

Hom.:

Cov.:

AF XY:

0.000553

AC XY:

317

AN XY:

573744

show subpopulations

Gnomad4 AFR exome

AF:

0.0000430

Gnomad4 AMR exome

AF:

0.000183

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000111

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000635

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.000322

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000277

Hom.:

Bravo

AF:

0.000257

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CLPTM1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 24, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

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