rs779188587
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1_ModeratePM2PP3_StrongPP5_Moderate
The NM_000789.4(ACE):c.3503+1G>A variant causes a splice donor change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_000789.4 splice_donor
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ACE | NM_000789.4 | c.3503+1G>A | splice_donor_variant | ENST00000290866.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ACE | ENST00000290866.10 | c.3503+1G>A | splice_donor_variant | 1 | NM_000789.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251128Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135832
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461682Hom.: 0 Cov.: 35 AF XY: 0.00000688 AC XY: 5AN XY: 727158
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
ACE-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 06, 2023 | The ACE c.3503+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant was reported in the compound heterozygous state in at least one individual with renal tubular dysgenesis (Gribouval et al 2012. PubMed ID: 22095942; Ruf K et al 2018. PubMed ID: 30598831). This variant is reported in 0.0098% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-61573878-G-A). Variants that disrupt the consensus splice donor site in ACE are expected to be pathogenic. This variant is interpreted as pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at