rs61749414
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000350.3(ABCA4):c.1903C>T(p.Gln635Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,042 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 (★★). Synonymous variant affecting the same amino acid position (i.e. Q635Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000350.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCA4 | NM_000350.3 | c.1903C>T | p.Gln635Ter | stop_gained | 13/50 | ENST00000370225.4 | |
ABCA4 | XM_047416704.1 | c.1903C>T | p.Gln635Ter | stop_gained | 13/49 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCA4 | ENST00000370225.4 | c.1903C>T | p.Gln635Ter | stop_gained | 13/50 | 1 | NM_000350.3 | P1 | |
ABCA4 | ENST00000649773.1 | c.1903C>T | p.Gln635Ter | stop_gained | 13/19 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461882Hom.: 0 Cov.: 37 AF XY: 0.00000413 AC XY: 3AN XY: 727244
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74324
ClinVar
Submissions by phenotype
not provided Pathogenic:2Other:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | This sequence change creates a premature translational stop signal (p.Gln635*) in the ABCA4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCA4 are known to be pathogenic (PMID: 10958761, 24938718, 25312043, 26780318). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ABCA4-related conditions (PMID: 10958763, 28559085, 29555955, 32531858). ClinVar contains an entry for this variant (Variation ID: 99096). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2018 | - - |
not provided, no classification provided | literature only | Retina International | - | - - |
Severe early-childhood-onset retinal dystrophy Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Medical Molecular Genetics, University of Zurich | Jan 30, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg | Jan 01, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at