9-136372011-G-C

Variant names:

• chr9-136372011-G-C
• NM_052813.5:c.68C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_052813.5(CARD9):​c.68C>G​(p.Ser23Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CARD9 NM_052813.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12

Genes affected

CARD9 (HGNC:16391): (caspase recruitment domain family member 9) The protein encoded by this gene is a member of the CARD protein family, which is defined by the presence of a characteristic caspase-associated recruitment domain (CARD). CARD is a protein interaction domain known to participate in activation or suppression of CARD containing members of the caspase family, and thus plays an important regulatory role in cell apoptosis. This protein was identified by its selective association with the CARD domain of BCL10, a postive regulator of apoptosis and NF-kappaB activation, and is thought to function as a molecular scaffold for the assembly of a BCL10 signaling complex that activates NF-kappaB. Several alternatively spliced transcript variants have been observed, but their full-length nature is not clearly defined. [provided by RefSeq, Jul 2008]

ENSG00000289701 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD9	NM_052813.5	c.68C>G	p.Ser23Trp	missense_variant	Exon 2 of 13	ENST00000371732.10	NP_434700.2
CARD9	NM_052814.4	c.68C>G	p.Ser23Trp	missense_variant	Exon 2 of 13		NP_434701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD9	ENST00000371732.10	c.68C>G	p.Ser23Trp	missense_variant	Exon 2 of 13	1	NM_052813.5	ENSP00000360797.5
ENSG00000289701	ENST00000696169.1	n.68C>G		non_coding_transcript_exon_variant	Exon 2 of 13			ENSP00000512460.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460486 Hom.: 0 Cov.: 82 AF XY: 0.00000138 AC XY: 1 AN XY: 726532

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	.;T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.023	D;D
Polyphen		1.0	D;D
Vest4		0.64
MutPred		0.60		Loss of disorder (P = 0.1126);Loss of disorder (P = 0.1126);
MVP		0.29
MPC		2.0
ClinPred		0.95	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-139266463;