9-136372044-C-G

Variant names:

• chr9-136372044-C-G
• NM_052813.5:c.35G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052813.5(CARD9):​c.35G>C​(p.Ser12Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S12N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: CARD9 NM_052813.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056955606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD9	NM_052813.5	c.35G>C	p.Ser12Thr	missense_variant	Exon 2 of 13	ENST00000371732.10	NP_434700.2
CARD9	NM_052814.4	c.35G>C	p.Ser12Thr	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.35G>C	p.Ser12Thr	missense_variant	Exon 2 of 13	1	NM_052813.5	ENSP00000360797.5
ENSG00000289701	ENST00000696169.1	n.35G>C		non_coding_transcript_exon_variant	Exon 2 of 13			ENSP00000512460.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 83

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.3
DANN	Benign	0.87
DEOGEN2	Benign	0.081	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.86	N;N
REVEL	Benign	0.030
Sift	Benign	0.12	T;T
Sift4G	Benign	0.71	T;T
Polyphen		0.023	B;B
Vest4		0.095
MutPred		0.54		Loss of disorder (P = 0.1169);Loss of disorder (P = 0.1169);
MVP		0.081
MPC		0.62
ClinPred		0.033	T
GERP RS		-0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.13

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: chr9-139266496;