rs1310569366

Variant names:

• chr15-41231433-CAAG-C
• rs1310569366
• NM_007236.5:c.55_57delAAG

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The NM_007236.5(CHP1):​c.55_57delAAG​(p.Lys19del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00000276 in 1,451,560 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: CHP1 NM_007236.5 conservative_inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.88

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_007236.5. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 15-41231433-CAAG-C is Pathogenic according to our data. Variant chr15-41231433-CAAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 632545.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHP1	NM_007236.5	c.55_57delAAG	p.Lys19del	conservative_inframe_deletion	Exon 1 of 7	ENST00000334660.10	NP_009167.1
CHP1	XM_017021879.3	c.55_57delAAG	p.Lys19del	conservative_inframe_deletion	Exon 1 of 5		XP_016877368.1
CHP1	XM_047432125.1	c.-122_-120delAAG		5_prime_UTR_variant	Exon 1 of 6		XP_047288081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHP1	ENST00000334660.10	c.55_57delAAG	p.Lys19del	conservative_inframe_deletion	Exon 1 of 7	1	NM_007236.5	ENSP00000335632.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1451560 Hom.: 0 AF XY: 0.00000277 AC XY: 2 AN XY: 720910

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000361

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spastic ataxia 9, autosomal recessive Pathogenic:1

Mar 04, 2025

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs1310569366; hg19: chr15-41523631;