rs371511979
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong
The NM_024589.3(ROGDI):āc.781T>Cā(p.Phe261Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000334 in 1,557,322 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. F261F) has been classified as Likely benign.
Frequency
Consequence
NM_024589.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ROGDI | NM_024589.3 | c.781T>C | p.Phe261Leu | missense_variant | 10/11 | ENST00000322048.12 | |
ROGDI | XM_006720947.5 | c.802T>C | p.Phe268Leu | missense_variant | 10/11 | ||
ROGDI | XM_047434636.1 | c.532T>C | p.Phe178Leu | missense_variant | 8/9 | ||
ROGDI | NR_046480.2 | n.788T>C | non_coding_transcript_exon_variant | 9/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROGDI | ENST00000322048.12 | c.781T>C | p.Phe261Leu | missense_variant | 10/11 | 1 | NM_024589.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000142 AC: 17AN: 120100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251256Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135850
GnomAD4 exome AF: 0.0000244 AC: 35AN: 1437136Hom.: 0 Cov.: 37 AF XY: 0.0000308 AC XY: 22AN XY: 714796
GnomAD4 genome ? AF: 0.000141 AC: 17AN: 120186Hom.: 0 Cov.: 32 AF XY: 0.000119 AC XY: 7AN XY: 58638
ClinVar
Submissions by phenotype
Amelocerebrohypohidrotic syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2021 | This sequence change replaces phenylalanine with leucine at codon 261 of the ROGDI protein (p.Phe261Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs371511979, ExAC 0.04%). 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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