chr16-74624030-C-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_018124.4(RFWD3):c.2223G>C(p.Gln741His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,613,940 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_018124.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RFWD3 | NM_018124.4 | c.2223G>C | p.Gln741His | missense_variant | 13/13 | ENST00000361070.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RFWD3 | ENST00000361070.9 | c.2223G>C | p.Gln741His | missense_variant | 13/13 | 1 | NM_018124.4 | P1 | |
RFWD3 | ENST00000571750.5 | c.2223G>C | p.Gln741His | missense_variant | 14/14 | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250942Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135632
GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461816Hom.: 2 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727216
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74308
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 21, 2021 | The c.2223G>C (p.Q741H) alteration is located in exon 13 (coding exon 12) of the RFWD3 gene. This alteration results from a G to C substitution at nucleotide position 2223, causing the glutamine (Q) at amino acid position 741 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 07, 2023 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with RFWD3-related conditions. This variant is present in population databases (rs763982760, gnomAD 0.002%). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 741 of the RFWD3 protein (p.Gln741His). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at