17-68984122-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_080283.4(ABCA9):c.4433C>T(p.Thr1478Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_080283.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCA9 | NM_080283.4 | c.4433C>T | p.Thr1478Ile | missense_variant | 35/39 | ENST00000340001.9 | NP_525022.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCA9 | ENST00000340001.9 | c.4433C>T | p.Thr1478Ile | missense_variant | 35/39 | 1 | NM_080283.4 | ENSP00000342216.3 | ||
ABCA9 | ENST00000453985.6 | c.4319C>T | p.Thr1440Ile | missense_variant | 34/38 | 5 | ENSP00000394264.2 | |||
ABCA9-AS1 | ENST00000630625.1 | n.378-27861G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251262Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135770
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727246
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74348
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 09, 2023 | The c.4433C>T (p.T1478I) alteration is located in exon 35 (coding exon 34) of the ABCA9 gene. This alteration results from a C to T substitution at nucleotide position 4433, causing the threonine (T) at amino acid position 1478 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at