rs750984782
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_003611.3(OFD1):c.2177G>A(p.Arg726His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000562 in 1,209,609 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 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 -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OFD1 | NM_003611.3 | c.2177G>A | p.Arg726His | missense_variant | 16/23 | ENST00000340096.11 | NP_003602.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OFD1 | ENST00000340096.11 | c.2177G>A | p.Arg726His | missense_variant | 16/23 | 1 | NM_003611.3 | ENSP00000344314.6 |
Frequencies
GnomAD3 genomes AF: 0.0000268 AC: 3AN: 111845Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34029
GnomAD3 exomes AF: 0.0000165 AC: 3AN: 181834Hom.: 0 AF XY: 0.0000298 AC XY: 2AN XY: 67022
GnomAD4 exome AF: 0.0000592 AC: 65AN: 1097764Hom.: 0 Cov.: 31 AF XY: 0.0000606 AC XY: 22AN XY: 363128
GnomAD4 genome AF: 0.0000268 AC: 3AN: 111845Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34029
ClinVar
Submissions by phenotype
Familial aplasia of the vermis;C1510460:Orofaciodigital syndrome I Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 27, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 726 of the OFD1 protein (p.Arg726His). This variant is present in population databases (rs750984782, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with OFD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 571012). 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 with a negative predictive value of 80%. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at