11-105041589-A-C

Position:

• chr11-105041589-A-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.*174T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,780 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CARD16 NM_052889.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.25

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=0.071765155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD16	NM_052889.4	c.*174T>G		3_prime_UTR_variant	4/4	ENST00000673097.2	NP_443121.1
CARD16	NM_001394580.1	c.*174T>G		3_prime_UTR_variant	4/4		NP_001381509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD16	ENST00000673097.2	c.*174T>G		3_prime_UTR_variant	4/4		NM_052889.4	ENSP00000509408
CARD16	ENST00000672037.1	c.405T>G	p.Asn135Lys	missense_variant	3/3			ENSP00000509530	P1
CARD16	ENST00000525374.1	n.485T>G		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461780 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727194

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.: 33

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

May 05, 2023

The c.405T>G (p.N135K) alteration is located in exon 3 (coding exon 3) of the CARD16 gene. This alteration results from a T to G substitution at nucleotide position 405, causing the asparagine (N) at amino acid position 135 to be replaced by a lysine (K). 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	0.22
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.17
DANN	Benign	0.73
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N;N;N;N
PROVEAN	Benign	0.36	N
REVEL	Benign	0.084
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.041	D
Polyphen		0.92	P
Vest4		0.12
MutPred		0.32		Loss of sheet (P = 0.0104);
MVP		0.061
MPC		0.23
ClinPred		0.13	T
GERP RS		-0.85
Varity_R		0.040
gMVP		0.091

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: chr11-104912316;