chr19-21536429-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001001415.4(ZNF429):āc.376T>Cā(p.Tyr126His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. Y126C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001001415.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF429 | NM_001001415.4 | c.376T>C | p.Tyr126His | missense_variant | 4/4 | ENST00000358491.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF429 | ENST00000358491.9 | c.376T>C | p.Tyr126His | missense_variant | 4/4 | 3 | NM_001001415.4 | P1 | |
ZNF429 | ENST00000597078.5 | c.227-5335T>C | intron_variant | 1 | |||||
ZNF429 | ENST00000594022.1 | n.761T>C | non_coding_transcript_exon_variant | 6/6 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 1AN: 151148Hom.: 0 Cov.: 33 FAILED QC
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461536Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727086
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000661 AC: 1AN: 151266Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 73906
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 17, 2023 | The c.376T>C (p.Y126H) alteration is located in exon 4 (coding exon 4) of the ZNF429 gene. This alteration results from a T to C substitution at nucleotide position 376, causing the tyrosine (Y) at amino acid position 126 to be replaced by a histidine (H). 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