chr17-63477097-G-T
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP5_Moderate
The NM_000789.4(ACE):c.3G>T(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000432 in 1,157,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_000789.4 start_lost
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACE | NM_000789.4 | c.3G>T | p.Met1? | start_lost | 1/25 | ENST00000290866.10 | |
ACE | NM_001382700.1 | c.-233G>T | 5_prime_UTR_variant | 1/22 | |||
ACE | NM_001382701.1 | c.-612G>T | 5_prime_UTR_variant | 1/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACE | ENST00000290866.10 | c.3G>T | p.Met1? | start_lost | 1/25 | 1 | NM_000789.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 0.00000432 AC: 5AN: 1157466Hom.: 0 Cov.: 29 AF XY: 0.00000713 AC XY: 4AN XY: 561298
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Renal tubular dysgenesis of genetic origin Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Neuberg Centre For Genomic Medicine, NCGM | - | The start lost variant c.3G>T (p.Met1?) in ACE gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. Null variant (start loss), in gene ACE for which loss-of-function is a known mechanism of disease. The variant is predicted to be damaging by SIFT and the residue is conserved across species. The nucleotide change in ACE is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.