chr16-57020800-G-A

Variant summary

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

The NM_001384950.1(NLRC5):​c.88G>A​(p.Ala30Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 28)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

NLRC5
NM_001384950.1 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0420
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]

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=0.032637626).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NLRC5NM_001384950.1 linkuse as main transcriptc.88G>A p.Ala30Thr missense_variant 3/49 ENST00000688547.1 NP_001371879.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NLRC5ENST00000688547.1 linkuse as main transcriptc.88G>A p.Ala30Thr missense_variant 3/49 NM_001384950.1 ENSP00000509992 P2Q86WI3-1

Frequencies

GnomAD3 genomes
AF:
0.00000662
AC:
1
AN:
151162
Hom.:
0
Cov.:
28
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000211
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000477
AC:
12
AN:
251450
Hom.:
0
AF XY:
0.0000662
AC XY:
9
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000116
AC:
17
AN:
1461878
Hom.:
0
Cov.:
32
AF XY:
0.0000179
AC XY:
13
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000661
AC:
1
AN:
151278
Hom.:
0
Cov.:
28
AF XY:
0.00
AC XY:
0
AN XY:
73864
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000211
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000370
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000659
AC:
8
Asia WGS
AF:
0.000577
AC:
2
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 submitterclinical testingAmbry GeneticsSep 01, 2021The c.88G>A (p.A30T) 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 88, causing the alanine (A) at amino acid position 30 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
0.077
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
8.4
DANN
Benign
0.96
DEOGEN2
Benign
0.0026
T;.;T;.
Eigen
Benign
-0.89
Eigen_PC
Benign
-0.98
FATHMM_MKL
Benign
0.081
N
LIST_S2
Benign
0.66
.;T;T;T
M_CAP
Benign
0.053
D
MetaRNN
Benign
0.033
T;T;T;T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
1.6
L;.;L;L
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-1.2
N;D;N;N
REVEL
Benign
0.087
Sift
Uncertain
0.014
D;D;D;D
Sift4G
Benign
0.063
T;T;T;T
Polyphen
0.38
B;.;B;.
Vest4
0.11
MutPred
0.22
Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);
MVP
0.16
MPC
0.24
ClinPred
0.022
T
GERP RS
-0.52
Varity_R
0.043
gMVP
0.17

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.

Other links and lift over

dbSNP: rs569522024; hg19: chr16-57054712; API