rs577731110

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

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

Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

CARD9
NM_052813.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.78

Publications

1 publications found

Variant links:

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]

CARD9 Gene-Disease associations (from GenCC):

deep dermatophytosis
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
predisposition to invasive fungal disease due to CARD9 deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

CARD9 links:

ENSG00000289701 (HGNC:):

ENSG00000289701 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052813.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARD9	NM_052813.5	MANE Select	c.1598C>T	p.Thr533Ile	missense	Exon 13 of 13	NP_434700.2
	CARD9	NM_052814.4		c.1442-153C>T		intron	N/A	NP_434701.1	Q9H257-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CARD9	ENST00000371732.10	TSL:1 MANE Select	c.1598C>T	p.Thr533Ile	missense	Exon 13 of 13	ENSP00000360797.5	Q9H257-1
ENSG00000289701	ENST00000696169.1		n.*1226C>T		non_coding_transcript_exon	Exon 12 of 13	ENSP00000512460.1
ENSG00000289701	ENST00000696169.1		n.*1226C>T		3_prime_UTR	Exon 12 of 13	ENSP00000512460.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000298

AC:

AN:

167728

AF XY:

0.0000448

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000743

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000284

AC:

AN:

1407568

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

695448

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32122

American (AMR)

AF:

0.00

AC:

AN:

36826

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25266

East Asian (EAS)

AF:

0.00

AC:

AN:

36824

South Asian (SAS)

AF:

0.00

AC:

AN:

80066

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47900

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0000369

AC:

AN:

1084506

Other (OTH)

AF:

0.00

AC:

AN:

58360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Predisposition to invasive fungal disease due to CARD9 deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Benign

0.17

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.81

M_CAP

Pathogenic

0.29

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.2

PhyloP100

4.8

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.61

REVEL

Benign

0.10

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0060

Polyphen

0.90

Vest4

0.57

MutPred

0.082

Loss of phosphorylation at T533 (P = 0.006)

MVP

0.62

MPC

0.36

ClinPred

0.29

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.50

Mutation Taster

=82/18

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over