rs139177611

Variant names:

• chrX-18757703-A-C
• rs139177611
• NM_001377996.1:c.473A>C

Your query was ambiguous. Multiple possible variants found:

• chrX-18757703-A-C
• chrX-18757703-A-G

Variant summary

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

The NM_001377996.1(PPEF1):​c.473A>C​(p.His158Pro) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H158R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: PPEF1 NM_001377996.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24885795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPEF1	NM_001377996.1	c.473A>C	p.His158Pro	missense_variant	Exon 5 of 16	ENST00000470157.2	NP_001364925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPEF1	ENST00000470157.2	c.473A>C	p.His158Pro	missense_variant	Exon 5 of 16	3	NM_001377996.1	ENSP00000419273.2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	16
DANN	Benign	0.75
DEOGEN2	Uncertain	0.61	D;.;T;.
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.63	T;T;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;M;.;.
PhyloP100		1.4
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-6.5	D;D;D;D
REVEL	Benign	0.065
Sift	Uncertain	0.025	D;D;T;T
Sift4G	Benign	0.23	T;T;T;T
Polyphen		0.93	P;P;.;.
Vest4		0.32
MutPred		0.34		Gain of disorder (P = 0.0818);Gain of disorder (P = 0.0818);.;.;
MVP		0.39
MPC		0.84
ClinPred		0.61	D
GERP RS		-0.54
Varity_R		0.51
gMVP		0.92
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs139177611; hg19: chrX-18775821;