19-21183750-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_133473.4(ZNF431):c.1447C>A(p.Pro483Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,613,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_133473.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF431 | NM_133473.4 | c.1447C>A | p.Pro483Thr | missense_variant | 5/5 | ENST00000311048.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF431 | ENST00000311048.11 | c.1447C>A | p.Pro483Thr | missense_variant | 5/5 | 1 | NM_133473.4 | P1 | |
ZNF431 | ENST00000600692.5 | c.*1034C>A | 3_prime_UTR_variant | 6/6 | 5 | ||||
ZNF431 | ENST00000594425.5 | c.97-6115C>A | intron_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152040Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000523 AC: 13AN: 248624Hom.: 0 AF XY: 0.0000667 AC XY: 9AN XY: 134912
GnomAD4 exome AF: 0.000125 AC: 182AN: 1461596Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 88AN XY: 727092
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152040Hom.: 0 Cov.: 33 AF XY: 0.0000808 AC XY: 6AN XY: 74282
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 22, 2021 | DNA sequence analysis of the ZNF431 gene demonstrated a sequence change, c.1450C>A, in exon 5 that results in an amino acid change, p.Pro484Thr. This sequence change has been described in the gnomAD database with a population frequency of 0.011% in the non-Finnish European subpopulation (dbSNP rs749228437). The p.Pro484Thr change affects a highly conserved amino acid residue located in a domain of the ZNF431 protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Pro484Thr substitution. This sequence change does not appear to have been previously described in patients with ZNF431-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Pro484Thr change remains unknown at this time - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at