rs886044731
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1
The NM_000350.3(ABCA4):c.3289A>T(p.Arg1097Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,890 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 Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R1097R) 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 Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCA4 | NM_000350.3 | c.3289A>T | p.Arg1097Ter | stop_gained | 22/50 | ENST00000370225.4 | |
ABCA4 | XM_047416704.1 | c.3067A>T | p.Arg1023Ter | stop_gained | 21/49 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCA4 | ENST00000370225.4 | c.3289A>T | p.Arg1097Ter | stop_gained | 22/50 | 1 | NM_000350.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727244
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 24, 2022 | ClinVar contains an entry for this variant (Variation ID: 242388). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Arg1097*) 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 premature translational stop signal has been observed in individual(s) with ABCA4-related conditions (PMID: 23982839, 28118664, 28559085). This variant is not present in population databases (gnomAD no frequency). - |
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at