22-37491203-C-T

Variant names:

• chr22-37491203-C-T
• NM_014550.4:c.3055G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014550.4(CARD10):​c.3055G>A​(p.Glu1019Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CARD10 NM_014550.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.17

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD10	NM_014550.4	c.3055G>A	p.Glu1019Lys	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.3055G>A	p.Glu1019Lys	missense_variant	Exon 20 of 20	1	NM_014550.4	ENSP00000251973.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1426220 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 706656

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: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.42	T;.;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	.;T;T
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.5	M;.;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.5	N;D;N
REVEL	Benign	0.27
Sift	Uncertain	0.010	D;D;D
Sift4G	Uncertain	0.014	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.77
MutPred		0.46		Gain of methylation at E1019 (P = 8e-04);.;Gain of methylation at E1019 (P = 8e-04);
MVP		0.75
MPC		0.75
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.43
gMVP		0.66

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: chr22-37887241;