NM_003392.7:c.1123G>A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_003392.7(WNT5A):c.1123G>A(p.Asp375Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_003392.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WNT5A | NM_003392.7 | c.1123G>A | p.Asp375Asn | missense_variant | Exon 5 of 5 | ENST00000264634.9 | NP_003383.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WNT5A | ENST00000264634.9 | c.1123G>A | p.Asp375Asn | missense_variant | Exon 5 of 5 | 1 | NM_003392.7 | ENSP00000264634.4 | ||
WNT5A | ENST00000474267.5 | c.1123G>A | p.Asp375Asn | missense_variant | Exon 6 of 6 | 5 | ENSP00000417310.1 | |||
WNT5A | ENST00000497027.5 | c.1078G>A | p.Asp360Asn | missense_variant | Exon 5 of 5 | 2 | ENSP00000420104.1 | |||
WNT5A | ENST00000493406.1 | n.30G>A | non_coding_transcript_exon_variant | Exon 1 of 2 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000722 AC: 11AN: 152250Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250888Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135652
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461718Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 727150
GnomAD4 genome AF: 0.0000722 AC: 11AN: 152250Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74392
ClinVar
Submissions by phenotype
Autosomal dominant Robinow syndrome 1 Uncertain:1
- -
not provided Uncertain:1
This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 375 of the WNT5A protein (p.Asp375Asn). This variant is present in population databases (rs763566950, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with WNT5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1023432). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt WNT5A protein function with a negative predictive value of 80%. 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