9-136364304-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_052813.5(CARD9):āc.1609T>Cā(p.Ter537Glnext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,556,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_052813.5 stop_lost
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.1609T>C | p.Ter537Glnext*? | stop_lost | Exon 13 of 13 | ENST00000371732.10 | NP_434700.2 | |
CARD9 | NM_052814.4 | c.1442-142T>C | intron_variant | Intron 12 of 12 | NP_434701.1 | |||
LOC124902309 | XR_007061863.1 | n.84+852A>G | intron_variant | Intron 1 of 1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CARD9 | ENST00000371732.10 | c.1609T>C | p.Ter537Glnext*? | stop_lost | Exon 13 of 13 | 1 | NM_052813.5 | ENSP00000360797.5 | ||
ENSG00000289701 | ENST00000696169.1 | n.*1237T>C | non_coding_transcript_exon_variant | Exon 12 of 13 | ENSP00000512460.1 | |||||
ENSG00000289701 | ENST00000696169.1 | n.*1237T>C | 3_prime_UTR_variant | Exon 12 of 13 | ENSP00000512460.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000613 AC: 1AN: 163252Hom.: 0 AF XY: 0.0000115 AC XY: 1AN XY: 86688
GnomAD4 exome AF: 0.0000107 AC: 15AN: 1404494Hom.: 0 Cov.: 32 AF XY: 0.0000144 AC XY: 10AN XY: 693526
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152172Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74334
ClinVar
Submissions by phenotype
Predisposition to invasive fungal disease due to CARD9 deficiency Uncertain:1
The CARD9 c.1609T>C (p.Ter537GlnextTer59) is a stop-lost variant, which was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. Due to the potential impact of stop-lost variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for familial candidiasis, recessive. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at