rs145718534
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_024589.3(ROGDI):c.78G>T(p.Glu26Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000461 in 1,519,912 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. E26Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_024589.3 missense
Scores
Clinical Significance
Conservation
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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.78G>T | p.Glu26Asp | missense_variant | 2/11 | ENST00000322048.12 | |
ROGDI | XM_006720947.5 | c.78G>T | p.Glu26Asp | missense_variant | 2/11 | ||
ROGDI | XM_047434636.1 | c.-138G>T | 5_prime_UTR_variant | 1/9 | |||
ROGDI | NR_046480.2 | n.140G>T | non_coding_transcript_exon_variant | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROGDI | ENST00000322048.12 | c.78G>T | p.Glu26Asp | missense_variant | 2/11 | 1 | NM_024589.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 151926Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 1AN: 125586Hom.: 0 AF XY: 0.0000141 AC XY: 1AN XY: 70686
GnomAD4 exome AF: 0.00000292 AC: 4AN: 1367986Hom.: 0 Cov.: 31 AF XY: 0.00000295 AC XY: 2AN XY: 677154
GnomAD4 genome AF: 0.0000197 AC: 3AN: 151926Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2AN XY: 74192
ClinVar
Submissions by phenotype
Amelocerebrohypohidrotic syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 25, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 26 of the ROGDI protein (p.Glu26Asp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ROGDI-related conditions. ClinVar contains an entry for this variant (Variation ID: 569223). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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