NM_006239.3:c.933+1009A>G

Variant names:

• chr4-75881917-T-C
• rs10518141
• NM_006239.3:c.933+1009A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

ENSG00000300740 (HGNC:58819):

LOC105377285 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006239.3. 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
	PPEF2	NM_006239.3	MANE Select	c.933+1009A>G		intron	N/A	NP_006230.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPEF2	ENST00000286719.12	TSL:1 MANE Select	c.933+1009A>G		intron	N/A	ENSP00000286719.6
	PPEF2	ENST00000511880.7	TSL:1	n.*585A>G		non_coding_transcript_exon	Exon 11 of 18	ENSP00000426186.2
	PPEF2	ENST00000511880.7	TSL:1	n.*585A>G		3_prime_UTR	Exon 11 of 18	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.160 AC: 6658 AN: 41538

American (AMR) AF: 0.0385 AC: 588 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0357 AC: 124 AN: 3470

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5194

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4826

European-Finnish (FIN) AF: 0.000941 AC: 10 AN: 10628

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.00409 AC: 278 AN: 68028

Other (OTH) AF: 0.0487 AC: 103 AN: 2116

Alfa AF: 0.0165 Hom.: 46

Bravo AF: 0.0579

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	10
DANN	Benign	0.84
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10518141; hg19: chr4-76803070;