rs375468265
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_130810.4(DNAAF4):āc.791A>Gā(p.His264Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,613,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_130810.4 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 |
---|---|---|---|---|---|---|---|
DNAAF4 | NM_130810.4 | c.791A>G | p.His264Arg | missense_variant | 7/10 | ENST00000321149.7 | |
DNAAF4-CCPG1 | NR_037923.1 | n.1046A>G | non_coding_transcript_exon_variant | 6/16 | |||
DNAAF4 | NM_001033560.2 | c.791A>G | p.His264Arg | missense_variant | 7/9 | ||
DNAAF4 | NM_001033559.3 | c.791A>G | p.His264Arg | missense_variant | 7/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF4 | ENST00000321149.7 | c.791A>G | p.His264Arg | missense_variant | 7/10 | 1 | NM_130810.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000179 AC: 45AN: 251242Hom.: 0 AF XY: 0.000206 AC XY: 28AN XY: 135836
GnomAD4 exome AF: 0.000213 AC: 312AN: 1461430Hom.: 0 Cov.: 30 AF XY: 0.000217 AC XY: 158AN XY: 727054
GnomAD4 genome ? AF: 0.000131 AC: 20AN: 152346Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14AN XY: 74502
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 28, 2022 | The c.791A>G (p.H264R) alteration is located in exon 7 (coding exon 6) of the DYX1C1 gene. This alteration results from a A to G substitution at nucleotide position 791, causing the histidine (H) at amino acid position 264 to be replaced by an arginine (R). 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 | Aug 15, 2022 | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 264 of the DNAAF4 protein (p.His264Arg). This variant is present in population databases (rs375468265, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with DNAAF4-related conditions. ClinVar contains an entry for this variant (Variation ID: 410961). 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 arginine 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