9-136364346-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_052813.5(CARD9):āc.1567G>Cā(p.Glu523Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00022 in 1,569,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_052813.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CARD9 | NM_052813.5 | c.1567G>C | p.Glu523Gln | missense_variant | Exon 13 of 13 | ENST00000371732.10 | NP_434700.2 | |
CARD9 | NM_052814.4 | c.1442-184G>C | intron_variant | Intron 12 of 12 | NP_434701.1 | |||
LOC124902309 | XR_007061863.1 | n.84+894C>G | intron_variant | Intron 1 of 1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CARD9 | ENST00000371732.10 | c.1567G>C | p.Glu523Gln | missense_variant | Exon 13 of 13 | 1 | NM_052813.5 | ENSP00000360797.5 | ||
ENSG00000289701 | ENST00000696169.1 | n.*1195G>C | non_coding_transcript_exon_variant | Exon 12 of 13 | ENSP00000512460.1 | |||||
ENSG00000289701 | ENST00000696169.1 | n.*1195G>C | 3_prime_UTR_variant | Exon 12 of 13 | ENSP00000512460.1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152232Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000121 AC: 22AN: 181824Hom.: 0 AF XY: 0.000103 AC XY: 10AN XY: 97560
GnomAD4 exome AF: 0.000231 AC: 327AN: 1416772Hom.: 0 Cov.: 32 AF XY: 0.000248 AC XY: 174AN XY: 700928
GnomAD4 genome AF: 0.000118 AC: 18AN: 152232Hom.: 0 Cov.: 34 AF XY: 0.000108 AC XY: 8AN XY: 74364
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.1567G>C (p.E523Q) alteration is located in exon 13 (coding exon 12) of the CARD9 gene. This alteration results from a G to C substitution at nucleotide position 1567, causing the glutamic acid (E) at amino acid position 523 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Predisposition to invasive fungal disease due to CARD9 deficiency Uncertain:1
This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 523 of the CARD9 protein (p.Glu523Gln). This variant is present in population databases (rs144943839, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CARD9-related conditions. ClinVar contains an entry for this variant (Variation ID: 646780). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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