chr16-74624026-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_018124.4(RFWD3):c.2227G>A(p.Asp743Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. 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_018124.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RFWD3 | NM_018124.4 | c.2227G>A | p.Asp743Asn | missense_variant | 13/13 | ENST00000361070.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RFWD3 | ENST00000361070.9 | c.2227G>A | p.Asp743Asn | missense_variant | 13/13 | 1 | NM_018124.4 | P1 | |
RFWD3 | ENST00000571750.5 | c.2227G>A | p.Asp743Asn | missense_variant | 14/14 | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251024Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135670
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461800Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727200
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74314
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 18, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 743 of the RFWD3 protein (p.Asp743Asn). This variant is present in population databases (rs775043994, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with RFWD3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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