chr16-4802386-A-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_024589.3(ROGDI):āc.113T>Gā(p.Leu38Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000211 in 1,418,598 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L38V) has been classified as Uncertain significance.
Frequency
Consequence
NM_024589.3 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 |
---|---|---|---|---|---|---|---|
ROGDI | NM_024589.3 | c.113T>G | p.Leu38Arg | missense_variant | 2/11 | ENST00000322048.12 | |
ROGDI | XM_006720947.5 | c.113T>G | p.Leu38Arg | missense_variant | 2/11 | ||
ROGDI | XM_047434636.1 | c.-103T>G | 5_prime_UTR_variant | 1/9 | |||
ROGDI | NR_046480.2 | n.175T>G | non_coding_transcript_exon_variant | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROGDI | ENST00000322048.12 | c.113T>G | p.Leu38Arg | missense_variant | 2/11 | 1 | NM_024589.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000211 AC: 3AN: 1418598Hom.: 0 Cov.: 31 AF XY: 0.00000284 AC XY: 2AN XY: 703980
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Amelocerebrohypohidrotic syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2020 | 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. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ROGDI-related disease. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces leucine with arginine at codon 38 of the ROGDI protein (p.Leu38Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at