Variant 11-105044505-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_052889.4(CARD16):c.161C>A(p.Thr54Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,830 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

CARD16
NM_052889.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.62

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]

CARD16 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD16	NM_052889.4 linkuse as main transcript	c.161C>A	p.Thr54Asn	missense_variant	2/4	ENST00000673097.2	NP_443121.1
CARD16	NM_001394580.1 linkuse as main transcript	c.113C>A	p.Thr38Asn	missense_variant	2/4		NP_001381509.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARD16	ENST00000673097.2 linkuse as main transcript	c.161C>A	p.Thr54Asn	missense_variant	2/4		NM_052889.4	ENSP00000509408		Q5EG05-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251344

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 30, 2023

The c.161C>A (p.T54N) alteration is located in exon 2 (coding exon 2) of the CARD16 gene. This alteration results from a C to A substitution at nucleotide position 161, causing the threonine (T) at amino acid position 54 to be replaced by an asparagine (N). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

T;.;.;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.36

LIST_S2

Uncertain

0.87

D;.;D;D

M_CAP

Benign

0.0035

MetaRNN

Uncertain

0.44

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N;N;.

MutationTaster

Benign

1.0

N;N;N;D

PROVEAN

Benign

-2.2

N;N;N;N

REVEL

Benign

0.19

Sift

Uncertain

0.0030

D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;.

Polyphen

0.76

P;P;P;.

Vest4

0.49

MutPred

0.72

Loss of phosphorylation at T54 (P = 0.1366);Loss of phosphorylation at T54 (P = 0.1366);Loss of phosphorylation at T54 (P = 0.1366);.;

MVP

0.43

MPC

0.62

ClinPred

0.43

GERP RS

3.3

Varity_R

0.27

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over