chr16-4802381-C-T
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1_ModeratePM2PP3_StrongPP5_Very_Strong
The NM_024589.3(ROGDI):c.117+1G>A variant causes a splice donor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000318 in 1,570,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_024589.3 splice_donor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ROGDI | NM_024589.3 | c.117+1G>A | splice_donor_variant | ENST00000322048.12 | |||
ROGDI | XM_006720947.5 | c.117+1G>A | splice_donor_variant | ||||
ROGDI | XM_047434636.1 | c.-99+1G>A | splice_donor_variant | ||||
ROGDI | NR_046480.2 | n.179+1G>A | splice_donor_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROGDI | ENST00000322048.12 | c.117+1G>A | splice_donor_variant | 1 | NM_024589.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000282 AC: 4AN: 1418102Hom.: 0 Cov.: 31 AF XY: 0.00000284 AC XY: 2AN XY: 703586
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74330
ClinVar
Submissions by phenotype
Amelocerebrohypohidrotic syndrome Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 15, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 30, 2021 | For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant is associated with skipping of exon 2 but is expected to preserve the integrity of the reading frame (PMID: 25565929). Disruption of this splice site has been observed in individual(s) with Kohlschütter-Tönz syndrome (PMID: 25565929). ClinVar contains an entry for this variant (Variation ID: 565630). This variant is present in population databases (rs570952151, ExAC 0.06%). This sequence change affects a donor splice site in intron 2 of the ROGDI gene. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at