9-136364315-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_052813.5(CARD9):c.1598C>T(p.Thr533Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000276 in 1,559,776 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_052813.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CARD9 | NM_052813.5 | c.1598C>T | p.Thr533Ile | missense_variant | Exon 13 of 13 | ENST00000371732.10 | NP_434700.2 | |
CARD9 | NM_052814.4 | c.1442-153C>T | intron_variant | Intron 12 of 12 | NP_434701.1 | |||
LOC124902309 | XR_007061863.1 | n.84+863G>A | intron_variant | Intron 1 of 1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CARD9 | ENST00000371732.10 | c.1598C>T | p.Thr533Ile | missense_variant | Exon 13 of 13 | 1 | NM_052813.5 | ENSP00000360797.5 | ||
ENSG00000289701 | ENST00000696169.1 | n.*1226C>T | non_coding_transcript_exon_variant | Exon 12 of 13 | ENSP00000512460.1 | |||||
ENSG00000289701 | ENST00000696169.1 | n.*1226C>T | 3_prime_UTR_variant | Exon 12 of 13 | ENSP00000512460.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152208Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000298 AC: 5AN: 167728Hom.: 0 AF XY: 0.0000448 AC XY: 4AN XY: 89322
GnomAD4 exome AF: 0.0000284 AC: 40AN: 1407568Hom.: 0 Cov.: 32 AF XY: 0.0000331 AC XY: 23AN XY: 695448
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152208Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74362
ClinVar
Submissions by phenotype
Predisposition to invasive fungal disease due to CARD9 deficiency Uncertain:1
This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 533 of the CARD9 protein (p.Thr533Ile). This variant is present in population databases (rs577731110, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with CARD9-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at