rs778246270
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2PP2BP4_ModerateBS2
The NM_014795.4(ZEB2):āc.1426A>Cā(p.Met476Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M476T) has been classified as Uncertain significance.
Frequency
Consequence
NM_014795.4 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZEB2 | NM_014795.4 | c.1426A>C | p.Met476Leu | missense_variant | 8/10 | ENST00000627532.3 | |
ZEB2 | NM_001171653.2 | c.1354A>C | p.Met452Leu | missense_variant | 7/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZEB2 | ENST00000627532.3 | c.1426A>C | p.Met476Leu | missense_variant | 8/10 | 1 | NM_014795.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250910Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135622
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461556Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727076
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Mowat-Wilson syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 02, 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. Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt ZEB2 function. ClinVar contains an entry for this variant (Variation ID: 534642). This variant has not been reported in the literature in individuals affected with ZEB2-related conditions. This variant is present in population databases (rs778246270, gnomAD 0.01%). This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 476 of the ZEB2 protein (p.Met476Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at