chr15-80180184-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000137.4(FAH):c.1021C>T(p.Arg341Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 1,609,844 control chromosomes in the GnomAD database, including 357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign,other (★★).
Frequency
Consequence
NM_000137.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FAH | NM_000137.4 | c.1021C>T | p.Arg341Trp | missense_variant | Exon 12 of 14 | ENST00000561421.6 | NP_000128.1 | |
FAH | NM_001374377.1 | c.1021C>T | p.Arg341Trp | missense_variant | Exon 13 of 15 | NP_001361306.1 | ||
FAH | NM_001374380.1 | c.1021C>T | p.Arg341Trp | missense_variant | Exon 13 of 15 | NP_001361309.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0157 AC: 2385AN: 152148Hom.: 26 Cov.: 32
GnomAD3 exomes AF: 0.0166 AC: 4096AN: 247378Hom.: 35 AF XY: 0.0162 AC XY: 2175AN XY: 134200
GnomAD4 exome AF: 0.0192 AC: 27949AN: 1457578Hom.: 331 Cov.: 32 AF XY: 0.0190 AC XY: 13773AN XY: 725322
GnomAD4 genome AF: 0.0157 AC: 2383AN: 152266Hom.: 26 Cov.: 32 AF XY: 0.0154 AC XY: 1143AN XY: 74458
ClinVar
Submissions by phenotype
not provided Benign:5Other:1
- Variant classified as "other reportable" ??? variant is clinically benign (not associated with disease) but is reported when observed (e.g. pseudodeficiency alleles).
- -
- -
FAH: BS1, BS2 -
This variant is associated with the following publications: (PMID: 29326876, 27153395, 27535533, 25087612, 25333069, 21228398, 7977370, 11278491) -
- -
Tyrosinemia type I Benign:3Other:2
- -
- -
A single pseudodeficiency allele, c.1021C>T (p.Arg341Trp), leads to decreased FAH enzyme activity and very little immunoreactive protein, but adequate amounts of FAH mRNA [Rootwelt et al 1994]. -
- pseudodeficiency allele
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Fumarylacetoacetase pseudodeficiency Pathogenic:1
- -
not specified Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at