chrX-18749853-C-T

Variant names:

• chrX-18749853-C-T
• rs150392543
• NM_001377996.1:c.297C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001377996.1(PPEF1):​c.297C>T​(p.Asp99Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000143 in 1,166,377 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 45 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00058 (0 hom., 13 hem., cov: 19)
  • Exomes 𝑓: 0.00010 (0 hom. 32 hem.)
• Consequence: PPEF1 NM_001377996.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.738
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant X-18749853-C-T is Benign according to our data. Variant chrX-18749853-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2660108.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.738 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 13 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377996.1. 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
	PPEF1	NM_001377996.1	MANE Select	c.297C>T	p.Asp99Asp	synonymous	Exon 4 of 16	NP_001364925.1	O14829-1
	PPEF1	NM_001377986.2		c.297C>T	p.Asp99Asp	synonymous	Exon 9 of 21	NP_001364915.1	O14829-1
	PPEF1	NM_001377993.1		c.297C>T	p.Asp99Asp	synonymous	Exon 6 of 18	NP_001364922.1	O14829-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPEF1	ENST00000470157.2	TSL:3 MANE Select	c.297C>T	p.Asp99Asp	synonymous	Exon 4 of 16	ENSP00000419273.2	O14829-1
	PPEF1	ENST00000361511.9	TSL:1	c.297C>T	p.Asp99Asp	synonymous	Exon 10 of 22	ENSP00000354871.3	O14829-1
	PPEF1	ENST00000471570.6	TSL:3	c.297C>T	p.Asp99Asp	synonymous	Exon 5 of 17	ENSP00000509623.1	O14829-1

Frequencies

GnomAD3 genomes AF: 0.000576 AC: 56 AN: 97187 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.00184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

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: 0.0000992

Gnomad OTH AF: 0.000787

GnomAD2 exomes AF: 0.000256 AC: 47 AN: 183408 AF XY: 0.000192

Gnomad AFR exome AF: 0.00182

Gnomad AMR exome AF: 0.000547

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000733

Gnomad OTH exome AF: 0.000442

GnomAD4 exome AF: 0.000104 AC: 111 AN: 1069169 Hom.: 0 Cov.: 29 AF XY: 0.0000932 AC XY: 32 AN XY: 343377

African (AFR) AF: 0.00206 AC: 53 AN: 25688

American (AMR) AF: 0.000520 AC: 18 AN: 34584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18672

East Asian (EAS) AF: 0.00 AC: 0 AN: 28779

South Asian (SAS) AF: 0.0000186 AC: 1 AN: 53691

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39007

Middle Eastern (MID) AF: 0.00100 AC: 4 AN: 3991

European-Non Finnish (NFE) AF: 0.0000207 AC: 17 AN: 820250

Other (OTH) AF: 0.000404 AC: 18 AN: 44507

GnomAD4 genome AF: 0.000576 AC: 56 AN: 97208 Hom.: 0 Cov.: 19 AF XY: 0.000528 AC XY: 13 AN XY: 24612

African (AFR) AF: 0.00183 AC: 47 AN: 25626

American (AMR) AF: 0.000392 AC: 3 AN: 7655

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2514

East Asian (EAS) AF: 0.00 AC: 0 AN: 2987

South Asian (SAS) AF: 0.00 AC: 0 AN: 1932

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3995

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 148

European-Non Finnish (NFE) AF: 0.0000992 AC: 5 AN: 50415

Other (OTH) AF: 0.000781 AC: 1 AN: 1281

Alfa AF: 0.000260 Hom.: 1

Bravo AF: 0.000597

EpiCase AF: 0.000219

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.26
PhyloP100		-0.74
Mutation Taster		=100/0	polymorphism

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: rs150392543; hg19: chrX-18767971; COSMIC: COSV62996872;