Variant 16-57025419-A-G 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.476A>G(p.Tyr159Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000561 in 1,426,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

NLRC5
NM_001384950.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.64

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:

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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=0.16187489).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRC5	NM_001384950.1 linkuse as main transcript	c.476A>G	p.Tyr159Cys	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.476A>G	p.Tyr159Cys	missense_variant	6/49		NM_001384950.1	ENSP00000509992	P2	Q86WI3-1
NLRC5	ENST00000262510.10 linkuse as main transcript	c.476A>G	p.Tyr159Cys	missense_variant	6/49	5		ENSP00000262510	P2	Q86WI3-1
NLRC5	ENST00000539144.5 linkuse as main transcript	c.476A>G	p.Tyr159Cys	missense_variant	4/46	5		ENSP00000441727	A2	Q86WI3-4
NLRC5	ENST00000539881.5 linkuse as main transcript	c.476A>G	p.Tyr159Cys	missense_variant, NMD_transcript_variant	6/25	2		ENSP00000441679		Q86WI3-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000273

AC:

AN:

219926

Hom.:

AF XY:

0.0000339

AC XY:

AN XY:

118110

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000228

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000199

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000561

AC:

AN:

1426958

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

707200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000456

Gnomad4 OTH exome

AF:

0.0000340

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

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

Aug 08, 2023

The c.476A>G (p.Y159C) alteration is located in exon 1 (coding exon 1) of the NLRC5 gene. This alteration results from a A to G substitution at nucleotide position 476, causing the tyrosine (Y) at amino acid position 159 to be replaced by a cysteine (C). 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

0.15

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

T;T;.

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.75

.;T;T

M_CAP

Benign

0.074

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.43

MutationAssessor

Benign

1.9

L;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-4.9

D;D;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

0.99

D;D;.

Vest4

0.23

MVP

0.46

MPC

0.34

ClinPred

0.31

GERP RS

3.0

Varity_R

0.19

gMVP

0.36

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