rs150774447
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP3_StrongPP5
The NM_000350.3(ABCA4):c.161G>T(p.Cys54Phe) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/23 in silico tools predict a damaging outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C54G) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000350.3 missense, splice_region
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCA4 | NM_000350.3 | c.161G>T | p.Cys54Phe | missense_variant, splice_region_variant | 3/50 | ENST00000370225.4 | NP_000341.2 | |
ABCA4 | XM_047416704.1 | c.161G>T | p.Cys54Phe | missense_variant, splice_region_variant | 3/49 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCA4 | ENST00000370225.4 | c.161G>T | p.Cys54Phe | missense_variant, splice_region_variant | 3/50 | 1 | NM_000350.3 | ENSP00000359245.3 | ||
ABCA4 | ENST00000649773.1 | c.161G>T | p.Cys54Phe | missense_variant, splice_region_variant | 3/19 | ENSP00000496882.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251396Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135878
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461872Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727236
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Severe early-childhood-onset retinal dystrophy Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | Department of Ophthalmology and Visual Sciences Kyoto University | - | - - |
not provided Other:1
not provided, no classification provided | literature only | Retina International | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at