11-105044524-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.05

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]

ACMG classification

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/exons	MANE	UniProt
CARD16	NM_052889.4	c.142G>T	p.Ala48Ser	missense_variant	2/4	ENST00000673097.2
CARD16	NM_001394580.1	c.94G>T	p.Ala32Ser	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARD16	ENST00000673097.2	c.142G>T	p.Ala48Ser	missense_variant	2/4		NM_052889.4

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2022

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;.
MutationTaster	Benign	1.0	N;N;N;N
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;