rs201116642
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_024589.3(ROGDI):c.584A>T(p.Asn195Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,728 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. N195S) has been classified as Uncertain significance.
Frequency
Consequence
NM_024589.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ROGDI | NM_024589.3 | c.584A>T | p.Asn195Ile | missense_variant | 8/11 | ENST00000322048.12 | |
ROGDI | XM_006720947.5 | c.584A>T | p.Asn195Ile | missense_variant | 8/11 | ||
ROGDI | XM_047434636.1 | c.314A>T | p.Asn105Ile | missense_variant | 6/9 | ||
ROGDI | NR_046480.2 | n.591A>T | non_coding_transcript_exon_variant | 7/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROGDI | ENST00000322048.12 | c.584A>T | p.Asn195Ile | missense_variant | 8/11 | 1 | NM_024589.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151976Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000800 AC: 2AN: 250058Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135514
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461752Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1AN XY: 727192
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151976Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74234
ClinVar
Submissions by phenotype
Amelocerebrohypohidrotic syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces asparagine with isoleucine at codon 195 of the ROGDI protein (p.Asn195Ile). The asparagine residue is highly conserved and there is a large physicochemical difference between asparagine and isoleucine. This variant is present in population databases (rs201116642, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with ROGDI-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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