rs10518141

Positions:

• chr4-75881917-T-C
• chr4-75881917-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006239.3(PPEF2):​c.933+1009A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0512 in 152,298 control chromosomes in the GnomAD database, including 546 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.051 (546 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: PPEF2 NM_006239.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210

Genes affected

PPEF2 (HGNC:9244): (protein phosphatase with EF-hand domain 2) 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, which is expressed specifically in photoreceptors and the pineal, has been suggested to play a role in the visual system. This gene shares high sequence similarity with the Drosophila retinal degeneration C (rdgC) gene. [provided by RefSeq, Jul 2008]

LOC105377285 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPEF2	NM_006239.3	c.933+1009A>G		intron_variant		ENST00000286719.12	NP_006230.2
PPEF2	XM_011532039.3	c.933+1009A>G		intron_variant			XP_011530341.1
LOC105377285	XR_938895.3	n.399+3142T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPEF2	ENST00000286719.12	c.933+1009A>G		intron_variant		1	NM_006239.3	ENSP00000286719.6
PPEF2	ENST00000511880.7	n.*585A>G		non_coding_transcript_exon_variant	11/18	1		ENSP00000426186.2
PPEF2	ENST00000511880.7	n.*585A>G		3_prime_UTR_variant	11/18	1		ENSP00000426186.2

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 7761 AN: 152180 Hom.: 539 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0386

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.00409

Gnomad OTH AF: 0.0492

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0512 AC: 7797 AN: 152298 Hom.: 546 Cov.: 32 AF XY: 0.0496 AC XY: 3695 AN XY: 74488

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.0385

Gnomad4 ASJ AF: 0.0357

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.000941

Gnomad4 NFE AF: 0.00409

Gnomad4 OTH AF: 0.0487

Alfa AF: 0.0118 Hom.: 31

Bravo AF: 0.0579

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	10
DANN	Benign	0.84

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: rs10518141; hg19: chr4-76803070;