rs1189655158
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4BS2_Supporting
The NM_003611.3(OFD1):c.1427C>T(p.Ala476Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000332 in 1,205,849 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_003611.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OFD1 | NM_003611.3 | c.1427C>T | p.Ala476Val | missense_variant | 14/23 | ENST00000340096.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OFD1 | ENST00000340096.11 | c.1427C>T | p.Ala476Val | missense_variant | 14/23 | 1 | NM_003611.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000917 AC: 1AN: 109060Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 31664
GnomAD3 exomes AF: 0.00000549 AC: 1AN: 182105Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 66743
GnomAD4 exome AF: 0.00000274 AC: 3AN: 1096789Hom.: 0 Cov.: 32 AF XY: 0.00000552 AC XY: 2AN XY: 362335
GnomAD4 genome ? AF: 0.00000917 AC: 1AN: 109060Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 31664
ClinVar
Submissions by phenotype
Familial aplasia of the vermis;C1510460:Orofaciodigital syndrome I Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 07, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt OFD1 protein function. ClinVar contains an entry for this variant (Variation ID: 463448). This variant has not been reported in the literature in individuals affected with OFD1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 476 of the OFD1 protein (p.Ala476Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at