16-57020990-C-G

Position:

• chr16-57020990-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001384950.1(NLRC5):​c.278C>G​(p.Thr93Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 28)
• Consequence: NLRC5 NM_001384950.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.509

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]

ACMG classification

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=0.059257716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NLRC5	NM_001384950.1	c.278C>G	p.Thr93Ser	missense_variant	3/49	ENST00000688547.1	NP_001371879.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NLRC5	ENST00000688547.1	c.278C>G	p.Thr93Ser	missense_variant	3/49		NM_001384950.1	ENSP00000509992	P2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 28

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2022

The c.278C>G (p.T93S) alteration is located in exon 1 (coding exon 1) of the NLRC5 gene. This alteration results from a C to G substitution at nucleotide position 278, causing the threonine (T) at amino acid position 93 to be replaced by a serine (S). 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	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.4
DANN	Benign	0.95
DEOGEN2	Benign	0.0029	T;T;.
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.70	.;T;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.059	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	L;L;L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.90	N;N;N
REVEL	Benign	0.039
Sift	Benign	0.56	T;T;T
Sift4G	Uncertain	0.032	D;D;D
Polyphen		0.085	B;B;.
Vest4		0.12
MutPred		0.30		Loss of glycosylation at T93 (P = 0.0613);Loss of glycosylation at T93 (P = 0.0613);Loss of glycosylation at T93 (P = 0.0613);
MVP		0.34
MPC		0.24
ClinPred		0.039	T
GERP RS		1.2
Varity_R		0.023
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-57054902;