11-105041702-C-G

Variant names:

• chr11-105041702-C-G
• rs1864115943
• NM_052889.4:c.*61G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052889.4(CARD16):​c.*61G>C variant causes a 3 prime UTR 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CARD16 NM_052889.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.300

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15627638).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARD16	NM_052889.4	c.*61G>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000673097.2	NP_443121.1
CARD16	NM_001394580.1	c.*61G>C		3_prime_UTR_variant	Exon 4 of 4		NP_001381509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARD16	ENST00000673097	c.*61G>C		3_prime_UTR_variant	Exon 4 of 4		NM_052889.4	ENSP00000509408.1
CARD16	ENST00000672037.1	c.292G>C	p.Asp98His	missense_variant	Exon 3 of 3			ENSP00000509530.1
CARD16	ENST00000528513.1	c.244G>C	p.Asp82His	missense_variant	Exon 3 of 3	3		ENSP00000510629.1
CARD16	ENST00000525374.1	n.372G>C		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 26, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.292G>C (p.D98H) alteration is located in exon 3 (coding exon 3) of the CARD16 gene. This alteration results from a G to C substitution at nucleotide position 292, causing the aspartic acid (D) at amino acid position 98 to be replaced by a histidine (H). 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	0.20
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	6.8
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;.
PROVEAN	Benign	-2.2	N;N
REVEL	Benign	0.073
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.0040	D;.
Polyphen		1.0	D;.
Vest4		0.18
MutPred		0.35		Gain of catalytic residue at N99 (P = 0.0868);.;
MVP		0.38
MPC		0.81
ClinPred		0.54	D
GERP RS		1.4
Varity_R		0.17
gMVP		0.14

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

Other links and lift over

dbSNP: rs1864115943; hg19: chr11-104912429;