chr22-37491245-G-C

Variant names:

• chr22-37491245-G-C
• NM_014550.4:c.3013C>G

Variant summary

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

The NM_014550.4(CARD10):​c.3013C>G​(p.Arg1005Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000707 in 1,414,398 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: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CARD10 NM_014550.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.50

Genes affected

CARD10 (HGNC:16422): (caspase recruitment domain family member 10) The caspase recruitment domain (CARD) is a protein module that consists of 6 or 7 antiparallel alpha helices. It participates in apoptosis signaling through highly specific protein-protein homophilic interactions. Like several other CARD proteins, CARD10 belongs to the membrane-associated guanylate kinase (MAGUK) family and activates NF-kappa-B (NFKB; see MIM 164011) through BCL10 (MIM 603517) (Wang et al., 2001 [PubMed 11259443]).[supplied by OMIM, Mar 2008]

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, 0.764

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD10	NM_014550.4	c.3013C>G	p.Arg1005Gly	missense_variant	Exon 20 of 20	ENST00000251973.10	NP_055365.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD10	ENST00000251973.10	c.3013C>G	p.Arg1005Gly	missense_variant	Exon 20 of 20	1	NM_014550.4	ENSP00000251973.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1414398 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 700286

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: 0.00

Gnomad4 OTH exome AF: 0.0000170

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D;.;D
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	.;D;D
M_CAP	Benign	0.062	D
MetaRNN	Pathogenic	0.76	D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.4	M;.;M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.6	D;D;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0040	D;D;D
Sift4G	Uncertain	0.0060	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.70
MutPred		0.53		Loss of MoRF binding (P = 0.0341);.;Loss of MoRF binding (P = 0.0341);
MVP		0.75
MPC		1.2
ClinPred		0.96	D
GERP RS		5.2
Varity_R		0.43
gMVP		0.73

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: chr22-37887283;