Variant 16-57025491-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001384950.1(NLRC5):c.548G>A(p.Arg183Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,266 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 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

NLRC5
NM_001384950.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.66

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 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=0.20507967).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRC5	NM_001384950.1 linkuse as main transcript	c.548G>A	p.Arg183Gln	missense_variant	6/49	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.548G>A	p.Arg183Gln	missense_variant	6/49		NM_001384950.1	ENSP00000509992	P2	Q86WI3-1
NLRC5	ENST00000262510.10 linkuse as main transcript	c.548G>A	p.Arg183Gln	missense_variant	6/49	5		ENSP00000262510	P2	Q86WI3-1
NLRC5	ENST00000539144.5 linkuse as main transcript	c.548G>A	p.Arg183Gln	missense_variant	4/46	5		ENSP00000441727	A2	Q86WI3-4
NLRC5	ENST00000539881.5 linkuse as main transcript	c.548G>A	p.Arg183Gln	missense_variant, NMD_transcript_variant	6/25	2		ENSP00000441679		Q86WI3-3

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250078

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135052

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461114

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726794

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000813

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

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 16, 2024

The c.548G>A (p.R183Q) alteration is located in exon 1 (coding exon 1) of the NLRC5 gene. This alteration results from a G to A substitution at nucleotide position 548, causing the arginine (R) at amino acid position 183 to be replaced by a glutamine (Q). 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

0.099

BayesDel_addAF

Benign

-0.089

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0027

T;T;.

Eigen

Benign

-0.012

Eigen_PC

Benign

-0.029

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.74

.;T;T

M_CAP

Benign

0.052

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.2

M;M;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.77

N;N;N

REVEL

Benign

0.19

Sift

Benign

0.43

T;T;T

Sift4G

Uncertain

0.026

D;D;D

Polyphen

0.90

P;P;.

Vest4

0.27

MutPred

0.46

Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);Gain of sheet (P = 0.0827);

MVP

0.58

MPC

0.61

ClinPred

0.76

GERP RS

2.8

Varity_R

0.043

gMVP

0.13

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