chr17-80189840-C-G

Position:

• chr17-80189840-C-G

Variant summary

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

The NM_001366385.1(CARD14):​c.931C>G​(p.Arg311Gly) 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. 12/21 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: 32)
• Consequence: CARD14 NM_001366385.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.265

Genes affected

CARD14 (HGNC:16446): (caspase recruitment domain family member 14) This gene encodes a caspase recruitment domain-containing protein that is a member of the membrane-associated guanylate kinase (MAGUK) family of proteins. Members of this protein family are scaffold proteins that are involved in a diverse array of cellular processes including cellular adhesion, signal transduction and cell polarity control. This protein has been shown to specifically interact with BCL10, a protein known to function as a positive regulator of cell apoptosis and NF-kappaB activation. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Apr 2012]

CARD14 (HGNC:):

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=0.24967816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD14	NM_001366385.1	c.931C>G	p.Arg311Gly	missense_variant	9/24	ENST00000648509.2	NP_001353314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD14	ENST00000648509.2	c.931C>G	p.Arg311Gly	missense_variant	9/24		NM_001366385.1	ENSP00000498071.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;.;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.75	.;.;T;T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;M;M;M
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.3	.;.;.;D
REVEL	Benign	0.12
Sift	Benign	0.031	.;.;.;D
Sift4G	Uncertain	0.021	D;.;D;D
Polyphen		0.83	P;P;.;P
Vest4		0.41
MutPred		0.42		Loss of MoRF binding (P = 0.0214);Loss of MoRF binding (P = 0.0214);Loss of MoRF binding (P = 0.0214);Loss of MoRF binding (P = 0.0214);
MVP		0.73
MPC		0.52
ClinPred		0.94	D
GERP RS		0.43
Varity_R		0.11
gMVP		0.27

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: rs145167842; hg19: chr17-78163639;