18-25092005-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_015461.3(ZNF521):āc.3735A>Gā(p.Ile1245Met) 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 1,461,738 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 (ā ).
Frequency
Consequence
NM_015461.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF521 | NM_015461.3 | c.3735A>G | p.Ile1245Met | missense_variant | 6/8 | ENST00000361524.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF521 | ENST00000361524.8 | c.3735A>G | p.Ile1245Met | missense_variant | 6/8 | 1 | NM_015461.3 | P1 | |
ZNF521 | ENST00000584787.5 | c.3075A>G | p.Ile1025Met | missense_variant | 5/7 | 1 | |||
ZNF521 | ENST00000399425.6 | c.*80A>G | 3_prime_UTR_variant, NMD_transcript_variant | 7/9 | 1 | ||||
ZNF521 | ENST00000538137.6 | c.3735A>G | p.Ile1245Met | missense_variant | 6/8 | 2 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461738Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727178
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 06, 2022 | The c.3735A>G (p.I1245M) alteration is located in exon 6 (coding exon 5) of the ZNF521 gene. This alteration results from a A to G substitution at nucleotide position 3735, causing the isoleucine (I) at amino acid position 1245 to be replaced by a methionine (M). 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