NM_006239.3:c.933+12T>C

Variant names:

• chr4-75882914-A-G
• rs4859564
• NM_006239.3:c.933+12T>C

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+12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.97 in 1,595,880 control chromosomes in the GnomAD database, including 759,006 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 0.86 (59439 hom., cov: 31)
  • Exomes 𝑓: 0.98 (699567 hom.)
• Consequence: PPEF2 NM_006239.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0740
• Publications: 8 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:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPEF2	NM_006239.3	c.933+12T>C		intron_variant	Intron 10 of 16	ENST00000286719.12	NP_006230.2
PPEF2	XM_011532039.3	c.933+12T>C		intron_variant	Intron 9 of 15		XP_011530341.1
LOC105377285	XR_938895.3	n.399+4139A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPEF2	ENST00000286719.12	c.933+12T>C		intron_variant	Intron 10 of 16	1	NM_006239.3	ENSP00000286719.6
PPEF2	ENST00000511880.7	n.*516+12T>C		intron_variant	Intron 10 of 17	1		ENSP00000426186.2

Frequencies

GnomAD3 genomes AF: 0.861 AC: 130945 AN: 152046 Hom.: 59433 Cov.: 31

Gnomad AFR AF: 0.538

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.949

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.990

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.994

Gnomad OTH AF: 0.889

GnomAD2 exomes AF: 0.957 AC: 228982 AN: 239254 AF XY: 0.967

Gnomad AFR exome AF: 0.528

Gnomad AMR exome AF: 0.964

Gnomad ASJ exome AF: 0.955

Gnomad EAS exome AF: 0.995

Gnomad FIN exome AF: 0.999

Gnomad NFE exome AF: 0.994

Gnomad OTH exome AF: 0.971

GnomAD4 exome AF: 0.982 AC: 1417188 AN: 1443716 Hom.: 699567 Cov.: 41 AF XY: 0.983 AC XY: 704387 AN XY: 716528

African (AFR) AF: 0.513 AC: 16634 AN: 32436

American (AMR) AF: 0.960 AC: 38978 AN: 40614

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 24350 AN: 25468

East Asian (EAS) AF: 0.997 AC: 39359 AN: 39464

South Asian (SAS) AF: 0.990 AC: 82403 AN: 83206

European-Finnish (FIN) AF: 0.999 AC: 53012 AN: 53072

Middle Eastern (MID) AF: 0.944 AC: 5349 AN: 5664

European-Non Finnish (NFE) AF: 0.996 AC: 1100083 AN: 1104192

Other (OTH) AF: 0.957 AC: 57020 AN: 59600

GnomAD4 genome AF: 0.861 AC: 130997 AN: 152164 Hom.: 59439 Cov.: 31 AF XY: 0.866 AC XY: 64397 AN XY: 74404

African (AFR) AF: 0.538 AC: 22278 AN: 41446

American (AMR) AF: 0.928 AC: 14170 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.949 AC: 3296 AN: 3472

East Asian (EAS) AF: 0.994 AC: 5153 AN: 5182

South Asian (SAS) AF: 0.990 AC: 4784 AN: 4832

European-Finnish (FIN) AF: 0.999 AC: 10604 AN: 10614

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.994 AC: 67655 AN: 68034

Other (OTH) AF: 0.887 AC: 1875 AN: 2114

Alfa AF: 0.915 Hom.: 9219

Bravo AF: 0.842

Asia WGS AF: 0.947 AC: 3293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.67
PhyloP100		-0.074
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: rs4859564; hg19: chr4-76804067;