rs72557938
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001395413.1(POR):c.842C>T(p.Pro281Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,612,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P281T) has been classified as Uncertain significance.
Frequency
Consequence
NM_001395413.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POR | NM_001395413.1 | c.842C>T | p.Pro281Leu | missense_variant | 9/16 | ENST00000461988.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POR | ENST00000461988.6 | c.842C>T | p.Pro281Leu | missense_variant | 9/16 | 1 | NM_001395413.1 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152082Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000482 AC: 12AN: 248974Hom.: 0 AF XY: 0.0000740 AC XY: 10AN XY: 135140
GnomAD4 exome AF: 0.0000459 AC: 67AN: 1460720Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 39AN XY: 726628
GnomAD4 genome AF: 0.0000395 AC: 6AN: 152082Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74296
ClinVar
Submissions by phenotype
POR-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 23, 2022 | The POR c.851C>T variant is predicted to result in the amino acid substitution p.Pro284Leu. To our knowledge, this variant has not been reported any individuals with a POR-related disorder. It has been identified in unaffected individuals, and functional studies suggest it may impact the activity of POR-P450 redox partner enzymes (Agrawal et al. 2008. PubMed ID: 18551037; Huang et al. 2008. PubMed ID: 18230729; Udhane et al. 2017. PubMed ID: 28970799). This variant is reported in 0.020% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-75612858-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at