Variant 16-57020780-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001384950.1(NLRC5):c.68A>C(p.Lys23Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,612,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

NLRC5
NM_001384950.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.465

Variant links:

Genes affected

NLRC5 (HGNC:29933): (NLR family CARD domain containing 5) This gene encodes a member of the caspase recruitment domain-containing NLR family. This gene plays a role in cytokine response and antiviral immunity through its inhibition of NF-kappa-B activation and negative regulation of type I interferon signaling pathways. [provided by RefSeq, Oct 2011]

NLRC5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.052832425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRC5	NM_001384950.1 linkuse as main transcript	c.68A>C	p.Lys23Thr	missense_variant	3/49	ENST00000688547.1	NP_001371879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRC5	ENST00000688547.1 linkuse as main transcript	c.68A>C	p.Lys23Thr	missense_variant	3/49		NM_001384950.1	ENSP00000509992	P2	Q86WI3-1

Frequencies

GnomAD3 genomes

AF:

0.000106

AC:

AN:

150796

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000195

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000265

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000443

Gnomad OTH

AF:

0.000487

GnomAD3 exomes

AF:

0.0000676

AC:

AN:

251452

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000224

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:

0.0000189

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.000106

AC:

AN:

150796

Hom.:

Cov.:

AF XY:

0.000136

AC XY:

AN XY:

73532

show subpopulations

Gnomad4 AFR

AF:

0.000195

Gnomad4 AMR

AF:

0.000265

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000443

Gnomad4 OTH

AF:

0.000487

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000128

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

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

Aug 02, 2022

The c.68A>C (p.K23T) alteration is located in exon 1 (coding exon 1) of the NLRC5 gene. This alteration results from a A to C substitution at nucleotide position 68, causing the lysine (K) at amino acid position 23 to be replaced by a threonine (T). 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

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0032

T;.;T;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.70

.;T;T;T

M_CAP

Benign

0.062

MetaRNN

Benign

0.053

T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.83

L;.;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.6

N;D;N;N

REVEL

Benign

0.13

Sift

Benign

0.12

T;T;T;T

Sift4G

Uncertain

0.0080

D;D;D;D

Polyphen

0.022

B;.;B;.

Vest4

0.19

MVP

0.27

MPC

0.30

ClinPred

0.0082

GERP RS

-0.35

Varity_R

0.069

gMVP

0.23

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