NM_006831.3:c.34A>G

Variant names:

• chr11-57659510-A-G
• rs1235734972
• NM_006831.3:c.34A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006831.3(CLP1):​c.34A>G​(p.Thr12Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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: 1.64
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 10

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.086066425).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006831.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLP1	NM_006831.3	MANE Select	c.34A>G	p.Thr12Ala	missense	Exon 2 of 3	NP_006822.1	Q92989-1
	CLP1	NM_001142597.2		c.34A>G	p.Thr12Ala	missense	Exon 2 of 3	NP_001136069.1	Q92989-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLP1	ENST00000533682.2	TSL:1 MANE Select	c.34A>G	p.Thr12Ala	missense	Exon 2 of 3	ENSP00000434995.1	Q92989-1
	CLP1	ENST00000525602.1	TSL:1	c.34A>G	p.Thr12Ala	missense	Exon 2 of 3	ENSP00000436066.1	Q92989-1
	CLP1	ENST00000529430.1	TSL:5	c.67A>G	p.Thr23Ala	missense	Exon 2 of 3	ENSP00000433406.1	E9PL17

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Benign	0.64
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		1.6
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.056
Sift	Benign	0.76	T
Sift4G	Benign	0.76	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.17		Loss of glycosylation at T12 (P = 0.0058)
MVP		0.46
MPC		0.60
ClinPred		0.041	T
GERP RS		3.0
Varity_R		0.021
gMVP		0.79
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1235734972; hg19: chr11-57426982;