X-48509902-C-T

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_203475.3(PORCN):​c.82C>T​(p.Gln28*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 22)

Consequence

PORCN
NM_203475.3 stop_gained

Scores

2
2
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.87
Variant links:
Genes affected
PORCN (HGNC:17652): (porcupine O-acyltransferase) This gene belongs to the evolutionarily conserved porcupine (Porc) gene family. Genes of the porcupine family encode endoplasmic reticulum proteins with multiple transmembrane domains. Porcupine proteins are involved in the processing of Wnt (wingless and int homologue) proteins. Disruption of this gene is associated with focal dermal hypoplasia, and the encoded protein has been implicated in cancer. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Aug 2013]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 51 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-48509902-C-T is Pathogenic according to our data. Variant chrX-48509902-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 694604.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PORCNNM_203475.3 linkc.82C>T p.Gln28* stop_gained Exon 2 of 15 ENST00000326194.11 NP_982301.1 Q9H237-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PORCNENST00000326194.11 linkc.82C>T p.Gln28* stop_gained Exon 2 of 15 1 NM_203475.3 ENSP00000322304.6 Q9H237-1

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
22

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Focal dermal hypoplasia Pathogenic:1
Oct 01, 2019
Laboratory of Research in Genomics, Genetics and Bioinformatics, Hospital Infantil de Mexico Federico Gomez
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: case-control

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.73
D
BayesDel_noAF
Pathogenic
0.62
CADD
Pathogenic
37
DANN
Uncertain
1.0
FATHMM_MKL
Uncertain
0.94
D
Vest4
0.78
GERP RS
4.6

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2061661896; hg19: chrX-48368290; API