Variant 16-57025406-G-A 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.463G>A(p.Ala155Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000887 in 1,559,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00092 ( 0 hom. )

Consequence

NLRC5
NM_001384950.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.367

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=0.019891828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NLRC5	NM_001384950.1 linkuse as main transcript	c.463G>A	p.Ala155Thr	missense_variant	6/49	ENST00000688547.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NLRC5	ENST00000688547.1 linkuse as main transcript	c.463G>A	p.Ala155Thr	missense_variant	6/49		NM_001384950.1	P2	Q86WI3-1
NLRC5	ENST00000262510.10 linkuse as main transcript	c.463G>A	p.Ala155Thr	missense_variant	6/49	5		P2	Q86WI3-1
NLRC5	ENST00000539144.5 linkuse as main transcript	c.463G>A	p.Ala155Thr	missense_variant	4/46	5		A2	Q86WI3-4
NLRC5	ENST00000539881.5 linkuse as main transcript	c.463G>A	p.Ala155Thr	missense_variant, NMD_transcript_variant	6/25	2			Q86WI3-3

Frequencies

GnomAD3 genomes

AF:

0.000565

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000567

AC:

117

AN:

206312

Hom.:

AF XY:

0.000564

AC XY:

AN XY:

109978

show subpopulations

Gnomad AFR exome

AF:

0.000316

Gnomad AMR exome

AF:

0.000545

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:

0.000957

Gnomad OTH exome

AF:

0.00123

GnomAD4 exome

AF:

0.000922

AC:

1297

AN:

1407302

Hom.:

Cov.:

AF XY:

0.000895

AC XY:

622

AN XY:

694902

show subpopulations

Gnomad4 AFR exome

AF:

0.000220

Gnomad4 AMR exome

AF:

0.000654

Gnomad4 ASJ exome

AF:

0.000227

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000646

Gnomad4 FIN exome

AF:

0.0000586

Gnomad4 NFE exome

AF:

0.00109

Gnomad4 OTH exome

AF:

0.000985

GnomAD4 genome

AF:

0.000565

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.000511

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00106

Hom.:

Bravo

AF:

0.000680

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000495

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

May 11, 2022

The c.463G>A (p.A155T) 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 463, causing the alanine (A) at amino acid position 155 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

0.082

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

Cadd

Benign

5.8

Dann

Benign

0.95

DEOGEN2

Benign

0.0046

T;T;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.052

M_CAP

Benign

0.030

MetaRNN

Benign

0.020

T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.4

L;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.065

Sift

Benign

0.28

T;T;T

Sift4G

Uncertain

0.023

D;D;D

Polyphen

0.0090

B;B;.

Vest4

0.026

MVP

0.26

MPC

0.24

ClinPred

0.0043

GERP RS

0.24

Varity_R

0.045

gMVP

0.078

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