rs1057519378

Positions:

• chr22-37516037-C-A
• chr22-37516037-C-T

Variant summary

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

The NM_014550.4(CARD10):​c.635G>T​(p.Arg212Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000179 in 1,450,220 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: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: CARD10 NM_014550.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.57

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, 0.787

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD10	NM_014550.4	c.635G>T	p.Arg212Leu	missense_variant	3/20	ENST00000251973.10	NP_055365.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD10	ENST00000251973.10	c.635G>T	p.Arg212Leu	missense_variant	3/20	1	NM_014550.4	ENSP00000251973.5
CARD10	ENST00000403299.5	c.635G>T	p.Arg212Leu	missense_variant	4/21	5		ENSP00000384570.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000436 AC: 1 AN: 229412 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 124736

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000982

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000179 AC: 26 AN: 1450220 Hom.: 0 Cov.: 32 AF XY: 0.0000125 AC XY: 9 AN XY: 720526

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: 0.0000235

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000508 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.70	D;D
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	.;D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.3	M;M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.8	D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0020	D;D
Sift4G	Benign	0.11	T;T
Polyphen		1.0	D;D
Vest4		0.70
MVP		0.65
MPC		1.0
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.59
gMVP		0.59

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

LitVar

Other links and lift over

dbSNP: rs1057519378; hg19: chr22-37912044;