11-105044421-T-C

Position:

• chr11-105044421-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_052889.4(CARD16):​c.245A>G​(p.Tyr82Cys) 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. 12/20 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: -0.869

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3978818).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD16	NM_052889.4	c.245A>G	p.Tyr82Cys	missense_variant	2/4	ENST00000673097.2	NP_443121.1
CARD16	NM_001394580.1	c.197A>G	p.Tyr66Cys	missense_variant	2/4		NP_001381509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD16	ENST00000673097.2	c.245A>G	p.Tyr82Cys	missense_variant	2/4		NM_052889.4	ENSP00000509408

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

Jun 30, 2023

The c.245A>G (p.Y82C) alteration is located in exon 2 (coding exon 2) of the CARD16 gene. This alteration results from a A to G substitution at nucleotide position 245, causing the tyrosine (Y) at amino acid position 82 to be replaced by a cysteine (C). 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	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.049	T;.;.;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.76	T;.;T;T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.40	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L;L;.
MutationTaster	Benign	1.0	N;N;N;N
PROVEAN	Pathogenic	-5.0	D;D;D;D
REVEL	Benign	0.097
Sift	Benign	0.036	D;T;T;T
Sift4G	Uncertain	0.056	T;T;T;.
Polyphen		0.99	D;D;D;.
Vest4		0.23
MutPred		0.40		Gain of catalytic residue at L83 (P = 0.011);Gain of catalytic residue at L83 (P = 0.011);Gain of catalytic residue at L83 (P = 0.011);.;
MVP		0.37
MPC		0.78
ClinPred		0.96	D
GERP RS		0.60
Varity_R		0.23
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-104915148;