rs786205119
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1_StrongPM2PP3_StrongPP5_Moderate
The NM_024589.3(ROGDI):c.532-2A>T variant causes a splice acceptor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,334 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 Pathogenic (★).
Frequency
Consequence
NM_024589.3 splice_acceptor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ROGDI | NM_024589.3 | c.532-2A>T | splice_acceptor_variant | ENST00000322048.12 | |||
ROGDI | XM_006720947.5 | c.532-2A>T | splice_acceptor_variant | ||||
ROGDI | XM_047434636.1 | c.262-2A>T | splice_acceptor_variant | ||||
ROGDI | NR_046480.2 | n.539-2A>T | splice_acceptor_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROGDI | ENST00000322048.12 | c.532-2A>T | splice_acceptor_variant | 1 | NM_024589.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 33
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460230Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0AN XY: 726444
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74292
ClinVar
Submissions by phenotype
Amelocerebrohypohidrotic syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Dec 16, 2022 | This variant was identified as compound heterozygous with NM_024589.3:c.531+5G>C._x000D_ Criteria applied: PVS1, PM3_VSTR, PM2_SUP - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 13, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at