18-25225282-A-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_015461.3(ZNF521):āc.2636T>Cā(p.Val879Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. V879I) has been classified as Uncertain significance.
Frequency
Consequence
NM_015461.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF521 | NM_015461.3 | c.2636T>C | p.Val879Ala | missense_variant | 4/8 | ENST00000361524.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF521 | ENST00000361524.8 | c.2636T>C | p.Val879Ala | missense_variant | 4/8 | 1 | NM_015461.3 | P1 | |
ZNF521 | ENST00000584787.5 | c.1976T>C | p.Val659Ala | missense_variant | 3/7 | 1 | |||
ZNF521 | ENST00000399425.6 | c.2636T>C | p.Val879Ala | missense_variant, NMD_transcript_variant | 4/9 | 1 | |||
ZNF521 | ENST00000538137.6 | c.2636T>C | p.Val879Ala | missense_variant | 4/8 | 2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251298Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135822
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461876Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 14AN XY: 727238
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2022 | The c.2636T>C (p.V879A) alteration is located in exon 4 (coding exon 3) of the ZNF521 gene. This alteration results from a T to C substitution at nucleotide position 2636, causing the valine (V) at amino acid position 879 to be replaced by an alanine (A). 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