11-57659602-A-T

Variant names:

• chr11-57659602-A-T
• NM_006831.3:c.126A>T
• CLP1 p.Ala42Ala

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006831.3(CLP1):​c.126A>T​(p.Ala42Ala) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A42A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLP1 NM_006831.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-1.25 with no splicing effect.

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.126A>T	p.Ala42Ala	synonymous	Exon 2 of 3	NP_006822.1	Q92989-1
	CLP1	NM_001142597.2		c.126A>T	p.Ala42Ala	synonymous	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.126A>T	p.Ala42Ala	synonymous	Exon 2 of 3	ENSP00000434995.1	Q92989-1
	CLP1	ENST00000525602.1	TSL:1	c.126A>T	p.Ala42Ala	synonymous	Exon 2 of 3	ENSP00000436066.1	Q92989-1
	CLP1	ENST00000529430.1	TSL:5	c.159A>T	p.Ala53Ala	synonymous	Exon 2 of 3	ENSP00000433406.1	E9PL17

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	3.4
DANN	Benign	0.62
PhyloP100		-1.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-57427074;