NM_172341.4:c.65G>A
Variant summary
Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_172341.4(PSENEN):c.65G>A(p.Gly22Glu) variant causes a missense change involving the alteration of a conserved nucleotide. 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 Uncertain significance (★).
Frequency
Consequence
NM_172341.4 missense
Scores
Clinical Significance
Conservation
Publications
- acne inversa, familial, 2Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- Dowling-Degos diseaseInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Likely_pathogenic. The variant received 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PSENEN | ENST00000587708.7 | c.65G>A | p.Gly22Glu | missense_variant | Exon 3 of 4 | 1 | NM_172341.4 | ENSP00000468411.1 | ||
PSENEN | ENST00000222266.2 | c.65G>A | p.Gly22Glu | missense_variant | Exon 3 of 4 | 1 | ENSP00000222266.1 | |||
ENSG00000188223 | ENST00000591613.2 | n.65G>A | non_coding_transcript_exon_variant | Exon 3 of 11 | 2 | ENSP00000468389.2 | ||||
PSENEN | ENST00000591949.1 | c.65G>A | p.Gly22Glu | missense_variant | Exon 3 of 3 | 2 | ENSP00000468593.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 22 of the PSENEN protein (p.Gly22Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PSENEN-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at