X-18779018-C-T

Variant names:

• chrX-18779018-C-T
• rs61733280
• NM_001377996.1:c.567C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001377996.1(PPEF1):​c.567C>T​(p.Leu189Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,194,298 control chromosomes in the GnomAD database, including 122 homozygotes. There are 1,262 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (58 hom., 590 hem., cov: 23)
  • Exomes 𝑓: 0.0024 (64 hom. 672 hem.)
• Consequence: PPEF1 NM_001377996.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.499
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant X-18779018-C-T is Benign according to our data. Variant chrX-18779018-C-T is described in ClinVar as [Benign]. Clinvar id is 714921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.499 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPEF1	NM_001377996.1	c.567C>T	p.Leu189Leu	synonymous_variant	Exon 7 of 16	ENST00000470157.2	NP_001364925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPEF1	ENST00000470157.2	c.567C>T	p.Leu189Leu	synonymous_variant	Exon 7 of 16	3	NM_001377996.1	ENSP00000419273.2

Frequencies

GnomAD3 genomes AF: 0.0201 AC: 2240 AN: 111169 Hom.: 58 Cov.: 23

Gnomad AFR AF: 0.0691

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00776

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000771

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00422

Gnomad NFE AF: 0.000396

Gnomad OTH AF: 0.0193

GnomAD2 exomes AF: 0.00619 AC: 1109 AN: 179135 AF XY: 0.00446

Gnomad AFR exome AF: 0.0742

Gnomad AMR exome AF: 0.00368

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000298

Gnomad OTH exome AF: 0.00317

GnomAD4 exome AF: 0.00236 AC: 2554 AN: 1083077 Hom.: 64 Cov.: 29 AF XY: 0.00191 AC XY: 672 AN XY: 352637

African (AFR) AF: 0.0749 AC: 1949 AN: 26011

American (AMR) AF: 0.00441 AC: 154 AN: 34924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19169

East Asian (EAS) AF: 0.00 AC: 0 AN: 30111

South Asian (SAS) AF: 0.000283 AC: 15 AN: 52993

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40426

Middle Eastern (MID) AF: 0.00341 AC: 14 AN: 4105

European-Non Finnish (NFE) AF: 0.000180 AC: 149 AN: 829738

Other (OTH) AF: 0.00599 AC: 273 AN: 45600

GnomAD4 genome AF: 0.0202 AC: 2249 AN: 111221 Hom.: 58 Cov.: 23 AF XY: 0.0176 AC XY: 590 AN XY: 33437

African (AFR) AF: 0.0692 AC: 2115 AN: 30544

American (AMR) AF: 0.00775 AC: 81 AN: 10450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3547

South Asian (SAS) AF: 0.000774 AC: 2 AN: 2584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5961

Middle Eastern (MID) AF: 0.00465 AC: 1 AN: 215

European-Non Finnish (NFE) AF: 0.000396 AC: 21 AN: 53072

Other (OTH) AF: 0.0191 AC: 29 AN: 1522

Alfa AF: 0.0118 Hom.: 69

Bravo AF: 0.0238

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 18, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	4.3
DANN	Benign	0.65
PhyloP100		-0.50
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: rs61733280; hg19: chrX-18797136;