chr22-37491203-C-G

Variant names:

• chr22-37491203-C-G
• rs200553561
• NM_014550.4:c.3055G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014550.4(CARD10):​c.3055G>C​(p.Glu1019Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000261 in 1,578,392 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00024 (1 hom.)
• Consequence: CARD10 NM_014550.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• 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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0058253706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD10	NM_014550.4	c.3055G>C	p.Glu1019Gln	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>C	p.Glu1019Gln	missense_variant	Exon 20 of 20	1	NM_014550.4	ENSP00000251973.5

Frequencies

GnomAD3 genomes AF: 0.000421 AC: 64 AN: 152056 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000464 AC: 88 AN: 189850 AF XY: 0.000454

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000800

Gnomad ASJ exome AF: 0.00217

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.000608

GnomAD4 exome AF: 0.000244 AC: 348 AN: 1426218 Hom.: 1 Cov.: 31 AF XY: 0.000286 AC XY: 202 AN XY: 706656

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 32946

Gnomad4 AMR exome AF: 0.00101 AC: 40 AN: 39766

Gnomad4 ASJ exome AF: 0.00138 AC: 35 AN: 25376

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 38262

Gnomad4 SAS exome AF: 0.000942 AC: 77 AN: 81754

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 46844

Gnomad4 NFE exome AF: 0.000147 AC: 161 AN: 1096428

Gnomad4 Remaining exome AF: 0.000524 AC: 31 AN: 59118

GnomAD4 genome AF: 0.000421 AC: 64 AN: 152174 Hom.: 0 Cov.: 31 AF XY: 0.000457 AC XY: 34 AN XY: 74390

Gnomad4 AFR AF: 0.000144 AC: 0.000144432 AN: 0.000144432

Gnomad4 AMR AF: 0.00196 AC: 0.00196053 AN: 0.00196053

Gnomad4 ASJ AF: 0.00173 AC: 0.00172811 AN: 0.00172811

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000622 AC: 0.000621633 AN: 0.000621633

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000235 AC: 0.000235301 AN: 0.000235301

Gnomad4 OTH AF: 0.000947 AC: 0.00094697 AN: 0.00094697

Alfa AF: 0.000381 Hom.: 0

Bravo AF: 0.000759

ExAC AF: 0.000364 AC: 43

Asia WGS AF: 0.000577 AC: 3 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

CARD10-related disorder Uncertain:1

Feb 05, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The CARD10 c.3055G>C variant is predicted to result in the amino acid substitution p.Glu1019Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.22% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;.;T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.75	.;T;T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.0058	T;T;T
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.5	M;.;M
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.16
Sift	Uncertain	0.013	D;D;D
Sift4G	Uncertain	0.018	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.75
MutPred		0.33		Gain of MoRF binding (P = 0.0279);.;Gain of MoRF binding (P = 0.0279);
MVP		0.73
MPC		0.57
ClinPred		0.083	T
GERP RS		5.3
Varity_R		0.33
gMVP		0.48
Mutation Taster		=79/21	polymorphism

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: rs200553561; hg19: chr22-37887241;