NM_001366385.1:c.1641G>T

Variant summary

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

The NM_001366385.1(CARD14):​c.1641G>T​(p.Arg547Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,218 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. R547R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CARD14
NM_001366385.1 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0340
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]

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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=0.021169335).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CARD14NM_001366385.1 linkc.1641G>T p.Arg547Ser missense_variant Exon 15 of 24 ENST00000648509.2 NP_001353314.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CARD14ENST00000648509.2 linkc.1641G>T p.Arg547Ser missense_variant Exon 15 of 24 NM_001366385.1 ENSP00000498071.1 Q9BXL6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461218
Hom.:
0
Cov.:
40
AF XY:
0.00
AC XY:
0
AN XY:
726936
show subpopulations
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.085
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
1.2
DANN
Benign
0.25
DEOGEN2
Benign
0.0031
T;T;.;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.19
.;.;T;T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.021
T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
-2.1
N;N;N;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
0.44
.;.;.;N
REVEL
Benign
0.017
Sift
Benign
0.59
.;.;.;T
Sift4G
Benign
0.83
T;.;T;T
Polyphen
0.0
B;B;.;B
Vest4
0.015
MutPred
0.31
Gain of phosphorylation at R547 (P = 0.017);Gain of phosphorylation at R547 (P = 0.017);Gain of phosphorylation at R547 (P = 0.017);Gain of phosphorylation at R547 (P = 0.017);
MVP
0.23
MPC
0.17
ClinPred
0.066
T
GERP RS
0.71
Varity_R
0.074
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-78171944; API