rs187082481
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_014967.5(FAN1):āc.1090A>Cā(p.Asn364His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,614,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_014967.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FAN1 | NM_014967.5 | c.1090A>C | p.Asn364His | missense_variant | 2/15 | ENST00000362065.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FAN1 | ENST00000362065.9 | c.1090A>C | p.Asn364His | missense_variant | 2/15 | 1 | NM_014967.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152176Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00101 AC: 253AN: 251448Hom.: 0 AF XY: 0.000802 AC XY: 109AN XY: 135892
GnomAD4 exome AF: 0.000190 AC: 278AN: 1461892Hom.: 0 Cov.: 34 AF XY: 0.000168 AC XY: 122AN XY: 727248
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74478
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 16, 2016 | The N364H variant in the FAN1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The N364H variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The N364H variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function. We interpret N364H as a variant of uncertain significance. - |
Karyomegalic interstitial nephritis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
FAN1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 21, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 09, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at