PPEF1 p.Leu189Leu

Variant names:

• chrX-18779015-T-T
• NM_001377996.1:c.

Your query was ambiguous. Multiple possible variants found:

• chrX-18779016--
• chrX-18779018-C-T
• chrX-18779018-C-A
• chrX-18779018-C-G
• chrX-18779016-CTC-TTA
• chrX-18779016-CTC-TTG

Variant summary

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

The NM_001377996.1(PPEF1):​c. variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 22)
• Consequence: PPEF1 NM_001377996.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.14
• Publications: 0 publications found

Genes affected

PPEF1 (HGNC:9243): (protein phosphatase with EF-hand domain 1) This gene encodes a member of the serine/threonine protein phosphatase with EF-hand motif family. The protein contains a protein phosphatase catalytic domain, and at least two EF-hand calcium-binding motifs in its C terminus. Although its substrate(s) is unknown, the encoded protein has been suggested to play a role in specific sensory neuron function and/or development. This gene shares high sequence similarity with the Drosophila retinal degeneration C (rdgC) gene. Several alternatively spliced transcript variants, each encoding a distinct isoform, have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377996.1. 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
	PPEF1	NM_001377996.1	MANE Select	c.		intron	N/A	NP_001364925.1	O14829-1
	PPEF1	NM_001377986.2		c.		intron	N/A	NP_001364915.1	O14829-1
	PPEF1	NM_001377993.1		c.		intron	N/A	NP_001364922.1	O14829-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPEF1	ENST00000470157.2	TSL:3 MANE Select	c.		splice_donor intron	N/A	ENSP00000419273.2	O14829-1
	PPEF1	ENST00000361511.9	TSL:1	c.		splice_donor intron	N/A	ENSP00000354871.3	O14829-1
	PPEF1	ENST00000471570.6	TSL:3	c.		splice_donor intron	N/A	ENSP00000509623.1	O14829-1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.1

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: chrX-18797133;