Variant 22-37491203-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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 (★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

CARD10
NM_014550.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.17

Variant links:

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]

CARD10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARD10	NM_014550.4 linkuse as main transcript	c.3055G>C	p.Glu1019Gln	missense_variant	20/20	ENST00000251973.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD10	ENST00000251973.10 linkuse as main transcript	c.3055G>C	p.Glu1019Gln	missense_variant	20/20	1	NM_014550.4	P1	Q9BWT7-1

Frequencies

GnomAD3 genomes

AF:

0.000421

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.000464

AC:

AN:

189850

Hom.:

AF XY:

0.000454

AC XY:

AN XY:

103616

show subpopulations

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 SAS exome

AF:

0.00118

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.:

Cov.:

AF XY:

0.000286

AC XY:

202

AN XY:

706656

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.00138

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000942

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000147

Gnomad4 OTH exome

AF:

0.000524

GnomAD4 genome

AF:

0.000421

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000381

Hom.:

Bravo

AF:

0.000759

ExAC

AF:

0.000364

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CARD10-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 05, 2024

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

BayesDel_noAF

Uncertain

-0.070

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.33

T;.;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.037

MetaRNN

Benign

0.0058

T;T;T

MetaSVM

Benign

-0.33

MutationAssessor

Uncertain

2.5

M;.;M

MutationTaster

Benign

0.93

D;D;D

PrimateAI

Uncertain

0.60

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

GERP RS

5.3

Varity_R

0.33

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over