chr11-57659780-C-G

Position:

• chr11-57659780-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006831.3(CLP1):​c.304C>G​(p.Gln102Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLP1 NM_006831.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.58

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36829105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLP1	NM_006831.3	c.304C>G	p.Gln102Glu	missense_variant	2/3	ENST00000533682.2	NP_006822.1
CLP1	NM_001142597.2	c.304C>G	p.Gln102Glu	missense_variant	2/3		NP_001136069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLP1	ENST00000533682.2	c.304C>G	p.Gln102Glu	missense_variant	2/3	1	NM_006831.3	ENSP00000434995.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2024

The c.304C>G (p.Q102E) alteration is located in exon 2 (coding exon 1) of the CLP1 gene. This alteration results from a C to G substitution at nucleotide position 304, causing the glutamine (Q) at amino acid position 102 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.028	T;T;.;T;.
Eigen	Benign	0.020
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	D;.;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.37	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;L;.;L;L
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.8	N;N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.26	T;T;T;T;T
Sift4G	Benign	0.54	T;T;T;T;T
Polyphen		0.058, 0.0040	.;B;.;B;B
Vest4		0.67
MutPred		0.35		.;Gain of helix (P = 0.005);Gain of helix (P = 0.005);Gain of helix (P = 0.005);Gain of helix (P = 0.005);
MVP		0.71
MPC		0.67
ClinPred		0.70	D
GERP RS		5.6
Varity_R		0.33
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-57427252;