chr22-37508609-G-C

Variant names:

• chr22-37508609-G-C
• rs139006752
• NM_014550.4:c.983C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014550.4(CARD10):​c.983C>G​(p.Ala328Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000421 in 1,426,622 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A328V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: CARD10 NM_014550.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.53
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 89 and autoimmunity

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 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.983C>G	p.Ala328Gly	missense_variant	Exon 5 of 20	ENST00000251973.10	NP_055365.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD10	ENST00000251973.10	c.983C>G	p.Ala328Gly	missense_variant	Exon 5 of 20	1	NM_014550.4	ENSP00000251973.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000421 AC: 6 AN: 1426622 Hom.: 0 Cov.: 32 AF XY: 0.00000565 AC XY: 4 AN XY: 707846

African (AFR) AF: 0.00 AC: 0 AN: 32986

American (AMR) AF: 0.00 AC: 0 AN: 40702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25568

East Asian (EAS) AF: 0.00 AC: 0 AN: 38256

South Asian (SAS) AF: 0.00 AC: 0 AN: 82884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42770

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.00000546 AC: 6 AN: 1098586

Other (OTH) AF: 0.00 AC: 0 AN: 59190

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.77	D;.;D
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	.;D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Uncertain	0.0085	D
MutationAssessor	Uncertain	2.0	M;.;M
PhyloP100		6.5
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-3.8	D;D;D
REVEL	Uncertain	0.43
Sift	Benign	0.031	D;D;D
Sift4G	Uncertain	0.058	T;T;T
Polyphen		0.045	B;.;B
Vest4		0.61
MutPred		0.11		Loss of stability (P = 0.1235);.;Loss of stability (P = 0.1235);
MVP		0.83
MPC		0.33
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.32
gMVP		0.61
Mutation Taster		=92/8	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

Other links and lift over

dbSNP: rs139006752; hg19: chr22-37904616;