X-18784036-A-G

Variant names:

• chrX-18784036-A-G
• rs61731650
• NM_001377996.1:c.900A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001377996.1(PPEF1):​c.900A>G​(p.Val300Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 1,196,150 control chromosomes in the GnomAD database, including 52 homozygotes. There are 800 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (34 hom., 415 hem., cov: 22)
  • Exomes 𝑓: 0.0013 (18 hom. 385 hem.)
• Consequence: PPEF1 NM_001377996.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.301
• Publications: 1 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=-0.82).
• BP6: Variant X-18784036-A-G is Benign according to our data. Variant chrX-18784036-A-G is described in ClinVar as [Benign]. Clinvar id is 713255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.301 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.014 (1571/112247) while in subpopulation AFR AF = 0.0485 (1496/30877). AF 95% confidence interval is 0.0464. There are 34 homozygotes in GnomAd4. There are 415 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 34 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPEF1	NM_001377996.1	c.900A>G	p.Val300Val	synonymous_variant	Exon 9 of 16	ENST00000470157.2	NP_001364925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPEF1	ENST00000470157.2	c.900A>G	p.Val300Val	synonymous_variant	Exon 9 of 16	3	NM_001377996.1	ENSP00000419273.2

Frequencies

GnomAD3 genomes AF: 0.0139 AC: 1565 AN: 112195 Hom.: 34 Cov.: 22

Gnomad AFR AF: 0.0484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00519

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: 0.0000751

Gnomad OTH AF: 0.0106

GnomAD2 exomes AF: 0.00392 AC: 670 AN: 170875 AF XY: 0.00234

Gnomad AFR exome AF: 0.0472

Gnomad AMR exome AF: 0.00210

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000510

Gnomad OTH exome AF: 0.00193

GnomAD4 exome AF: 0.00133 AC: 1437 AN: 1083903 Hom.: 18 Cov.: 29 AF XY: 0.00110 AC XY: 385 AN XY: 351351

African (AFR) AF: 0.0459 AC: 1191 AN: 25923

American (AMR) AF: 0.00268 AC: 87 AN: 32430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18776

East Asian (EAS) AF: 0.00 AC: 0 AN: 29901

South Asian (SAS) AF: 0.0000596 AC: 3 AN: 50376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40267

Middle Eastern (MID) AF: 0.000738 AC: 3 AN: 4067

European-Non Finnish (NFE) AF: 0.0000191 AC: 16 AN: 836658

Other (OTH) AF: 0.00301 AC: 137 AN: 45505

GnomAD4 genome AF: 0.0140 AC: 1571 AN: 112247 Hom.: 34 Cov.: 22 AF XY: 0.0121 AC XY: 415 AN XY: 34399

African (AFR) AF: 0.0485 AC: 1496 AN: 30877

American (AMR) AF: 0.00518 AC: 55 AN: 10620

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2652

East Asian (EAS) AF: 0.00 AC: 0 AN: 3576

South Asian (SAS) AF: 0.00 AC: 0 AN: 2714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6109

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.0000751 AC: 4 AN: 53262

Other (OTH) AF: 0.0104 AC: 16 AN: 1533

Alfa AF: 0.00651 Hom.: 36

Bravo AF: 0.0161

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 14, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.8
DANN	Benign	0.60
PhyloP100		0.30
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: rs61731650; hg19: chrX-18802154;