Variant 11-105044557-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_052889.4(CARD16):c.109C>A(p.Gln37Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000318 in 1,613,878 control chromosomes in the GnomAD database, including 4 homozygotes. 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 (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 4 hom. )

Consequence

CARD16
NM_052889.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.027168423).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARD16	NM_052889.4 linkuse as main transcript	c.109C>A	p.Gln37Lys	missense_variant	2/4	ENST00000673097.2	NP_443121.1
CARD16	NM_001394580.1 linkuse as main transcript	c.61C>A	p.Gln21Lys	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.109C>A	p.Gln37Lys	missense_variant	2/4		NM_052889.4	ENSP00000509408		Q5EG05-2

Frequencies

GnomAD3 genomes

AF:

0.000579

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.000771

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000358

AC:

AN:

251312

Hom.:

AF XY:

0.000331

AC XY:

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.000707

Gnomad SAS exome

AF:

0.000360

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000290

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000291

AC:

426

AN:

1461652

Hom.:

Cov.:

AF XY:

0.000286

AC XY:

208

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.000498

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.000510

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000224

Gnomad4 OTH exome

AF:

0.000414

GnomAD4 genome

AF:

0.000578

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000843

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.000773

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000382

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000347

Hom.:

Bravo

AF:

0.000506

ExAC

AF:

0.000552

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

Mar 16, 2022

The c.109C>A (p.Q37K) 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 109, causing the glutamine (Q) at amino acid position 37 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

0.052

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.037

T;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.34

T;.;T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.027

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;M;M;.

MutationTaster

Benign

1.0

N;N;N;N

PROVEAN

Uncertain

-2.8

D;D;D;D

REVEL

Benign

0.068

Sift

Benign

0.12

T;T;T;T

Sift4G

Benign

0.17

T;T;T;.

Polyphen

0.044

B;B;B;.

Vest4

0.24

MVP

0.23

MPC

0.35

ClinPred

0.011

GERP RS

0.19

Varity_R

0.38

gMVP

0.15

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

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