17-80181464-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001366385.1(CARD14):​c.26C>T​(p.Ser9Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,428,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CARD14
NM_001366385.1 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.239
Variant links:
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]

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=0.056690484).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CARD14NM_001366385.1 linkc.26C>T p.Ser9Phe missense_variant Exon 5 of 24 ENST00000648509.2 NP_001353314.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CARD14ENST00000648509.2 linkc.26C>T p.Ser9Phe missense_variant Exon 5 of 24 NM_001366385.1 ENSP00000498071.1 Q9BXL6-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000101
AC:
2
AN:
197670
Hom.:
0
AF XY:
0.00000940
AC XY:
1
AN XY:
106430
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000679
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000140
AC:
2
AN:
1428966
Hom.:
0
Cov.:
32
AF XY:
0.00000141
AC XY:
1
AN XY:
707846
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000498
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.:
33
ExAC
AF:
0.0000166
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Pityriasis rubra pilaris;C1864497:Psoriasis 2 Uncertain:1
Aug 02, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 9 of the CARD14 protein (p.Ser9Phe). This variant is present in population databases (rs779622128, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CARD14-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
21
DANN
Benign
0.74
DEOGEN2
Benign
0.086
T;T;T;.;.;T
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.043
N
LIST_S2
Benign
0.76
.;.;.;T;T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.057
T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
.;M;M;.;M;M
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-1.2
.;.;.;.;.;N
REVEL
Benign
0.052
Sift
Uncertain
0.021
.;.;.;.;.;D
Sift4G
Benign
0.25
T;T;.;T;T;T
Polyphen
0.32
.;B;B;.;.;B
Vest4
0.32, 0.33
MutPred
0.34
Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);
MVP
0.83
MPC
0.45
ClinPred
0.12
T
GERP RS
0.95
Varity_R
0.051
gMVP
0.53

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.

Other links and lift over

dbSNP: rs779622128; hg19: chr17-78155263; API