1-94019691-C-T
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM1PM5PP3_ModeratePP5_Very_Strong
The NM_000350.3(ABCA4):c.5087G>A(p.Ser1696Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,613,676 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1696R) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000350.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCA4 | NM_000350.3 | c.5087G>A | p.Ser1696Asn | missense_variant | 36/50 | ENST00000370225.4 | |
ABCA4 | XM_047416704.1 | c.4865G>A | p.Ser1622Asn | missense_variant | 35/49 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCA4 | ENST00000370225.4 | c.5087G>A | p.Ser1696Asn | missense_variant | 36/50 | 1 | NM_000350.3 | P1 | |
ABCA4 | ENST00000460514.1 | n.581G>A | non_coding_transcript_exon_variant | 7/7 | 5 | ||||
ABCA4 | ENST00000470771.1 | n.197G>A | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152192Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000399 AC: 10AN: 250460Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135352
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461484Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 726974
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152192Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3AN XY: 74344
ClinVar
Submissions by phenotype
not provided Pathogenic:2Other:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2023 | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1696 of the ABCA4 protein (p.Ser1696Asn). This variant is present in population databases (rs61750564, gnomAD 0.02%). This missense change has been observed in individuals with Stargardt disease (PMID: 18854780, 20128570, 24409374, 29854428). ClinVar contains an entry for this variant (Variation ID: 99344). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ABCA4 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. - |
not provided, no classification provided | literature only | Retina International | - | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Nov 20, 2020 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 9973280, 31589614, 29854428, 28044389, 28118664, 24409374, 19265867, 18854780, 28365912, 18652558, 25097154, 22076985, 21873672, 19324865) - |
Severe early-childhood-onset retinal dystrophy Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg | Jan 01, 2016 | - - |
Severe early-childhood-onset retinal dystrophy;C1858806:Cone-rod dystrophy 3;C1866422:Retinitis pigmentosa 19;C3495438:Age related macular degeneration 2 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 08, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at