rs768604345

Variant names:

• chr22-37491199-C-A
• rs768604345
• NM_014550.4:c.3059G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-37491199-C-A
• chr22-37491199-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014550.4(CARD10):​c.3059G>T​(p.Cys1020Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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: 0.273

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08599317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD10	NM_014550.4	c.3059G>T	p.Cys1020Phe	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.3059G>T	p.Cys1020Phe	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: 1424734 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 705786

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

ExAC AF: 0.00000846 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.4
DANN	Benign	0.88
DEOGEN2	Benign	0.072	T;.;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.58	.;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.086	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.;L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.77	N;N;N
REVEL	Benign	0.023
Sift	Benign	0.094	T;T;T
Sift4G	Benign	0.11	T;T;T
Polyphen		0.0060	B;.;B
Vest4		0.097
MutPred		0.47		Loss of disorder (P = 0.0695);.;Loss of disorder (P = 0.0695);
MVP		0.19
MPC		0.52
ClinPred		0.11	T
GERP RS		3.2
Varity_R		0.12
gMVP		0.20

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: rs768604345; hg19: chr22-37887237;