Genetic Variant IFI16:p.Pro284Thr (chr1-159018529-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001376587.1(IFI16):c.850C>A(p.Pro284Thr) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P284S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

IFI16
NM_001376587.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.79

Publications

0 publications found

Variant links:

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]

IFI16 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12735614).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376587.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFI16	NM_001376587.1	MANE Select	c.850C>A	p.Pro284Thr	missense	Exon 5 of 12	NP_001363516.1	Q16666-1
IFI16	NM_001364867.2		c.850C>A	p.Pro284Thr	missense	Exon 6 of 13	NP_001351796.1	Q16666-1
IFI16	NM_001206567.2		c.682C>A	p.Pro228Thr	missense	Exon 4 of 11	NP_001193496.1	Q16666-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFI16	ENST00000295809.12	TSL:5 MANE Select	c.850C>A	p.Pro284Thr	missense	Exon 5 of 12	ENSP00000295809.7	Q16666-1
IFI16	ENST00000368131.8	TSL:1	c.850C>A	p.Pro284Thr	missense	Exon 5 of 11	ENSP00000357113.4	Q16666-2
IFI16	ENST00000368132.7	TSL:1	c.850C>A	p.Pro284Thr	missense	Exon 5 of 11	ENSP00000357114.3	Q16666-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.031

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.022

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0027

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.7

PhyloP100

-1.8

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-5.2

REVEL

Benign

0.031

Sift

Benign

0.15

Sift4G

Benign

0.084

Polyphen

0.043

Vest4

0.20

MutPred

0.56

Gain of catalytic residue at P284 (P = 0.0876)

MVP

0.23

MPC

0.32

ClinPred

0.17

GERP RS

-2.6

Varity_R

0.19

gMVP

0.026

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over