19-44131036-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_013362.4(ZNF225):c.422T>C(p.Ile141Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,948 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I141F) has been classified as Uncertain significance.
Frequency
Consequence
NM_013362.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZNF225 | ENST00000262894.11 | c.422T>C | p.Ile141Thr | missense_variant | Exon 5 of 5 | 1 | NM_013362.4 | ENSP00000262894.5 | ||
ZNF225 | ENST00000590612.1 | c.422T>C | p.Ile141Thr | missense_variant | Exon 4 of 4 | 1 | ENSP00000468686.1 | |||
ZNF225 | ENST00000592780.5 | c.*203T>C | 3_prime_UTR_variant | Exon 6 of 6 | 5 | ENSP00000466889.1 | ||||
ZNF225 | ENST00000589155.5 | c.*55T>C | downstream_gene_variant | 4 | ENSP00000466853.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152222Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249762Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135490
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461726Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 727150
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152222Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74370
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.422T>C (p.I141T) alteration is located in exon 5 (coding exon 4) of the ZNF225 gene. This alteration results from a T to C substitution at nucleotide position 422, causing the isoleucine (I) at amino acid position 141 to be replaced by a threonine (T). 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