chr22-42619789-C-T
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM1BP4_StrongBP6BS1BS2
The NM_000398.7(CYB5R3):c.890G>A(p.Arg297His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,587,798 control chromosomes in the GnomAD database, including 13 homozygotes. 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000398.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYB5R3 | NM_000398.7 | c.890G>A | p.Arg297His | missense_variant | 9/9 | ENST00000352397.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYB5R3 | ENST00000352397.10 | c.890G>A | p.Arg297His | missense_variant | 9/9 | 1 | NM_000398.7 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00158 AC: 240AN: 152144Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00209 AC: 434AN: 208038Hom.: 2 AF XY: 0.00237 AC XY: 266AN XY: 112172
GnomAD4 exome AF: 0.00230 AC: 3301AN: 1435536Hom.: 13 Cov.: 32 AF XY: 0.00247 AC XY: 1761AN XY: 711722
GnomAD4 genome AF: 0.00158 AC: 241AN: 152262Hom.: 0 Cov.: 33 AF XY: 0.00167 AC XY: 124AN XY: 74450
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | CYB5R3: BS2 - |
Neurodevelopmental delay Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Kariminejad - Najmabadi Pathology & Genetics Center | Sep 22, 2018 | - - |
CYB5R3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 14, 2023 | 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at