Variant 16-57025397-C-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_001384950.1(NLRC5):c.454C>T(p.Arg152Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000358 in 1,396,174 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

NLRC5
NM_001384950.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14

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 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
NLRC5	NM_001384950.1 link	c.454C>T	p.Arg152Trp	missense_variant	6/49	ENST00000688547.1	NP_001371879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NLRC5	ENST00000688547.1 link	c.454C>T	p.Arg152Trp	missense_variant	6/49		NM_001384950.1	ENSP00000509992.1	Q86WI3-1
NLRC5	ENST00000262510.10 link	c.454C>T	p.Arg152Trp	missense_variant	6/49	5		ENSP00000262510.6	Q86WI3-1
NLRC5	ENST00000539144.5 link	c.454C>T	p.Arg152Trp	missense_variant	4/46	5		ENSP00000441727.1	Q86WI3-4
NLRC5	ENST00000539881.5 link	n.454C>T		non_coding_transcript_exon_variant	6/25	2		ENSP00000441679.1	Q86WI3-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000358

AC:

AN:

1396174

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

688180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.0000132

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000278

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 21, 2024

The c.454C>T (p.R152W) alteration is located in exon 1 (coding exon 1) of the NLRC5 gene. This alteration results from a C to T substitution at nucleotide position 454, causing the arginine (R) at amino acid position 152 to be replaced by a tryptophan (W). 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

0.21

BayesDel_addAF

Uncertain

0.037

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;T;.

Eigen

Benign

0.057

Eigen_PC

Benign

-0.0014

FATHMM_MKL

Benign

0.56

LIST_S2

Uncertain

0.92

.;D;D

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.43

T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Uncertain

2.1

M;M;M

PrimateAI

Benign

0.30

PROVEAN

Pathogenic

-4.5

D;D;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.014

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.35

MutPred

0.60

Loss of disorder (P = 0.0228);Loss of disorder (P = 0.0228);Loss of disorder (P = 0.0228);

MVP

0.50

MPC

0.84

ClinPred

0.97

GERP RS

3.0

Varity_R

0.14

gMVP

0.40

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