chr11-105044524-C-A

Variant summary

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

The NM_052889.4(CARD16):​c.142G>T​(p.Ala48Ser) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CARD16
NM_052889.4 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.05
Variant links:
Genes affected
CARD16 (HGNC:33701): (caspase recruitment domain family member 16) Enables several functions, including CARD domain binding activity; cysteine-type endopeptidase inhibitor activity; and enzyme binding activity. Involved in several processes, including negative regulation of cysteine-type endopeptidase activity; regulation of gene expression; and regulation of signal transduction. Part of protease inhibitor complex. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.052188486).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CARD16NM_052889.4 linkc.142G>T p.Ala48Ser missense_variant Exon 2 of 4 ENST00000673097.2 NP_443121.1 Q5EG05-2
CARD16NM_001394580.1 linkc.94G>T p.Ala32Ser missense_variant Exon 2 of 4 NP_001381509.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CARD16ENST00000673097.2 linkc.142G>T p.Ala48Ser missense_variant Exon 2 of 4 NM_052889.4 ENSP00000509408.1 Q5EG05-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 14, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.142G>T (p.A48S) alteration is located in exon 2 (coding exon 2) of the CARD16 gene. This alteration results from a G to T substitution at nucleotide position 142, causing the alanine (A) at amino acid position 48 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
0.046
DANN
Benign
0.50
DEOGEN2
Benign
0.021
T;.;.;.
Eigen
Benign
-2.0
Eigen_PC
Benign
-2.1
FATHMM_MKL
Benign
0.014
N
LIST_S2
Benign
0.17
T;.;T;T
M_CAP
Benign
0.0020
T
MetaRNN
Benign
0.052
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;L;L;.
PROVEAN
Benign
-0.84
N;N;N;N
REVEL
Benign
0.11
Sift
Benign
0.64
T;T;T;T
Sift4G
Benign
0.34
T;T;T;.
Polyphen
0.15
B;B;B;.
Vest4
0.13
MutPred
0.29
Gain of phosphorylation at A48 (P = 0.018);Gain of phosphorylation at A48 (P = 0.018);Gain of phosphorylation at A48 (P = 0.018);.;
MVP
0.17
MPC
0.24
ClinPred
0.38
T
GERP RS
-6.7
Varity_R
0.041
gMVP
0.067

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr11-104915251; API