NM_001377996.1:c.1335T>A

Variant names:

• chrX-18806486-T-A
• rs749073725
• NM_001377996.1:c.1335T>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001377996.1(PPEF1):​c.1335T>A​(p.Thr445Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000897 in 111,431 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T445T) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 23)
• Consequence: PPEF1 NM_001377996.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.305
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.305 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPEF1	NM_001377996.1	c.1335T>A	p.Thr445Thr	synonymous_variant	Exon 12 of 16	ENST00000470157.2	NP_001364925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPEF1	ENST00000470157.2	c.1335T>A	p.Thr445Thr	synonymous_variant	Exon 12 of 16	3	NM_001377996.1	ENSP00000419273.2

Frequencies

GnomAD3 genomes AF: 0.00000897 AC: 1 AN: 111431 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000897 AC: 1 AN: 111431 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33617

African (AFR) AF: 0.0000326 AC: 1 AN: 30657

American (AMR) AF: 0.00 AC: 0 AN: 10408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2648

East Asian (EAS) AF: 0.00 AC: 0 AN: 3564

South Asian (SAS) AF: 0.00 AC: 0 AN: 2639

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5969

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53119

Other (OTH) AF: 0.00 AC: 0 AN: 1510

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.40
PhyloP100		-0.30

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: rs749073725; hg19: chrX-18824604;