16-78164213-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_016373.4(WWOX):c.440A>G(p.His147Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,614,098 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_016373.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WWOX | NM_016373.4 | c.440A>G | p.His147Arg | missense_variant | Exon 5 of 9 | ENST00000566780.6 | NP_057457.1 | |
WWOX | NM_001291997.2 | c.101A>G | p.His34Arg | missense_variant | Exon 4 of 8 | NP_001278926.1 | ||
WWOX | NM_130791.5 | c.440A>G | p.His147Arg | missense_variant | Exon 5 of 6 | NP_570607.1 | ||
WWOX | NR_120436.3 | n.679A>G | non_coding_transcript_exon_variant | Exon 5 of 6 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000281 AC: 7AN: 249400Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135310
GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461812Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22AN XY: 727206
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152286Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74460
ClinVar
Submissions by phenotype
Autosomal recessive spinocerebellar ataxia 12;C3463992:Developmental and epileptic encephalopathy, 1 Uncertain:1
This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 147 of the WWOX protein (p.His147Arg). This variant is present in population databases (rs188859796, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of WWOX-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 410082). 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). 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. -
Inborn genetic diseases Uncertain:1
The c.440A>G (p.H147R) alteration is located in exon 5 (coding exon 5) of the WWOX gene. This alteration results from a A to G substitution at nucleotide position 440, causing the histidine (H) at amino acid position 147 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at