rs1057517410
Variant summary
Our verdict is Pathogenic. Variant got 22 ACMG points: 22P and 0B. PVS1PM2PP3_StrongPP5_Very_Strong
The NM_000159.4(GCDH):c.853-2A>G variant causes a splice acceptor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,198 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_000159.4 splice_acceptor
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 22 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GCDH | NM_000159.4 | c.853-2A>G | splice_acceptor_variant | ENST00000222214.10 | |||
GCDH | NM_013976.5 | c.853-2A>G | splice_acceptor_variant | ||||
GCDH | NR_102316.1 | n.1016-2A>G | splice_acceptor_variant, non_coding_transcript_variant | ||||
GCDH | NR_102317.1 | n.1234-2A>G | splice_acceptor_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GCDH | ENST00000222214.10 | c.853-2A>G | splice_acceptor_variant | 1 | NM_000159.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1459198Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726058
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Glutaric aciduria, type 1 Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 23, 2023 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Nov 01, 2016 | - - |
Pathogenic, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Mar 17, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at