15-41278827-AGG-CGT

Variant names:

• chr15-41278827-AGG-CGT
• NM_007236.5:c.472_474delAGGinsCGT
• CHP1 p.159

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_007236.5(CHP1):​c.472_474delAGGinsCGT​(p.159) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R158R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHP1 NM_007236.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0
• Publications: 0 publications found

Genes affected

CHP1 (HGNC:17433): (calcineurin like EF-hand protein 1) This gene encodes a phosphoprotein that binds to the Na+/H+ exchanger NHE1. This protein serves as an essential cofactor which supports the physiological activity of NHE family members and may play a role in the mitogenic regulation of NHE1. The protein shares similarity with calcineurin B and calmodulin and it is also known to be an endogenous inhibitor of calcineurin activity. [provided by RefSeq, Jul 2008]

CHP1 Gene-Disease associations (from GenCC):

• spastic ataxia 9, autosomal recessive

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007236.5. 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
	CHP1	NM_007236.5	MANE Select	c.472_474delAGGinsCGT	p.159	synonymous	N/A	NP_009167.1	Q99653

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHP1	ENST00000334660.10	TSL:1 MANE Select	c.472_474delAGGinsCGT	p.159	synonymous	N/A	ENSP00000335632.5	Q99653
	CHP1	ENST00000560411.5	TSL:1	n.*237_*239delAGGinsCGT		non_coding_transcript_exon	Exon 5 of 6	ENSP00000453375.1	H0YLX1
	CHP1	ENST00000560411.5	TSL:1	n.*237_*239delAGGinsCGT		3_prime_UTR	Exon 5 of 6	ENSP00000453375.1	H0YLX1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		10

Splicing

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: chr15-41571025;