chr1-159018555-T-G

Position:

• chr1-159018555-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001376587.1(IFI16):​c.876T>G​(p.Asn292Lys) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFI16 NM_001376587.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -5.01

Genes affected

IFI16 (HGNC:5395): (interferon gamma inducible protein 16) This gene encodes a member of the HIN-200 (hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats) family of cytokines. The encoded protein contains domains involved in DNA binding, transcriptional regulation, and protein-protein interactions. The protein localizes to the nucleoplasm and nucleoli, and interacts with p53 and retinoblastoma-1. It modulates p53 function, and inhibits cell growth in the Ras/Raf signaling pathway. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2011]

ACMG classification

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=0.16174242).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFI16	NM_001376587.1	c.876T>G	p.Asn292Lys	missense_variant	5/12	ENST00000295809.12	NP_001363516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFI16	ENST00000295809.12	c.876T>G	p.Asn292Lys	missense_variant	5/12	5	NM_001376587.1	ENSP00000295809	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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 29, 2023

The c.876T>G (p.N292K) alteration is located in exon 5 (coding exon 4) of the IFI16 gene. This alteration results from a T to G substitution at nucleotide position 876, causing the asparagine (N) at amino acid position 292 to be replaced by a lysine (K). 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	0.16
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.072
DANN	Benign	0.30
DEOGEN2	Benign	0.0097	.;.;T;.;.;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.29	.;T;T;T;T;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.16	T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.42	N;N;N;.;N;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.1	N;N;N;N;N;N
REVEL	Benign	0.058
Sift	Benign	0.70	T;T;T;T;T;T
Sift4G	Benign	0.91	T;T;T;T;T;T
Polyphen		0.0050	B;B;B;.;.;.
Vest4		0.15
MutPred		0.73		Gain of methylation at N292 (P = 0.014);Gain of methylation at N292 (P = 0.014);Gain of methylation at N292 (P = 0.014);.;Gain of methylation at N292 (P = 0.014);.;
MVP		0.13
MPC		0.56
ClinPred		0.039	T
GERP RS		-6.2
Varity_R		0.25
gMVP		0.023

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-158988345;