rs1555441703
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000137.4(FAH):c.835del(p.Gln279ArgfsTer25) variant causes a frameshift, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Q279Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000137.4 frameshift, splice_region
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 |
---|---|---|---|---|---|---|---|
FAH | NM_000137.4 | c.835del | p.Gln279ArgfsTer25 | frameshift_variant, splice_region_variant | 9/14 | ENST00000561421.6 | |
FAH | NM_001374377.1 | c.835del | p.Gln279ArgfsTer25 | frameshift_variant, splice_region_variant | 10/15 | ||
FAH | NM_001374380.1 | c.835del | p.Gln279ArgfsTer25 | frameshift_variant, splice_region_variant | 10/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FAH | ENST00000561421.6 | c.835del | p.Gln279ArgfsTer25 | frameshift_variant, splice_region_variant | 9/14 | 1 | NM_000137.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727248
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Tyrosinemia type I Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Mar 16, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at