Genetic Variant CLP1:p.Thr98Ile (chr11-57659769-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006831.3(CLP1):c.293C>T(p.Thr98Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,614,208 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

CLP1
NM_006831.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.77

Variant links:

Genes affected

CLP1 (HGNC:16999): (cleavage factor polyribonucleotide kinase subunit 1) This gene encodes a member of the Clp1 family. The encoded protein is a multifunctional kinase which is a component of the tRNA splicing endonuclease complex and a component of the pre-mRNA cleavage complex II. This protein is implicated in tRNA, mRNA, and siRNA maturation. Mutations in this gene are associated with pontocerebellar hypoplasia type 10 (PCH10). Alternatively splice transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

CLP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1190809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLP1	NM_006831.3 link	c.293C>T	p.Thr98Ile	missense_variant	Exon 2 of 3	ENST00000533682.2	NP_006822.1	Q92989-1
CLP1	NM_001142597.2 link	c.293C>T	p.Thr98Ile	missense_variant	Exon 2 of 3		NP_001136069.1	Q92989-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLP1	ENST00000533682.2 link	c.293C>T	p.Thr98Ile	missense_variant	Exon 2 of 3	1	NM_006831.3	ENSP00000434995.1		Q92989-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.0000437

AC:

AN:

251478

Hom.:

AF XY:

0.0000809

AC XY:

AN XY:

135916

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:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000233

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.000947

Bravo

AF:

0.00000756

ExAC

AF:

0.0000494

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

T;T;.;T;.

Eigen

Benign

-0.10

Eigen_PC

Benign

0.14

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;.;D;D;D

M_CAP

Benign

0.0070

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.090

.;N;.;N;N

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.1

N;N;N;N;N

REVEL

Benign

0.036

Sift

Benign

0.081

T;T;T;T;T

Sift4G

Uncertain

0.051

T;T;T;T;T

Polyphen

0.079, 0.060

.;B;.;B;B

Vest4

0.58

MutPred

0.40

.;Loss of disorder (P = 0.0284);Loss of disorder (P = 0.0284);Loss of disorder (P = 0.0284);Loss of disorder (P = 0.0284);

MVP

0.33

MPC

0.68

ClinPred

0.13

GERP RS

5.6

Varity_R

0.076

gMVP

0.56

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over