Variant chr14-94116511-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130080.3(IFI27):c.353T>C(p.Ile118Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

IFI27
NM_001130080.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0980

Variant links:

Genes affected

IFI27 (HGNC:5397): (interferon alpha inducible protein 27) Enables RNA polymerase II-specific DNA-binding transcription factor binding activity; identical protein binding activity; and lamin binding activity. Involved in several processes, including cellular protein metabolic process; defense response to other organism; and extrinsic apoptotic signaling pathway. Acts upstream of or within negative regulation of transcription by RNA polymerase II and regulation of protein export from nucleus. Located in mitochondrial membrane and nuclear inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

IFI27 links:

IFI27 (HGNC:):

IFI27 links:

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ACMG classification

Classification made for transcript

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=0.12816778).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
IFI27	NM_001130080.3 linkuse as main transcript	c.353T>C	p.Ile118Thr	missense_variant	5/5	NP_001123552.1	P40305-2
IFI27	NM_001288952.2 linkuse as main transcript	c.353T>C	p.Ile118Thr	missense_variant	6/6	NP_001275881.1	P40305-2
IFI27	NM_001288956.2 linkuse as main transcript	c.353T>C	p.Ile118Thr	missense_variant	5/5	NP_001275885.1	P40305-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFI27	ENST00000621160.5 linkuse as main transcript	c.353T>C	p.Ile118Thr	missense_variant	5/5	1		ENSP00000483498.1		P40305-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

249050

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134514

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460924

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726622

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000595

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

Aug 01, 2024

The c.344T>C (p.I115T) alteration is located in exon 5 (coding exon 4) of the IFI27 gene. This alteration results from a T to C substitution at nucleotide position 344, causing the isoleucine (I) at amino acid position 115 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

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.51

CADD

Benign

3.2

DANN

Benign

0.54

DEOGEN2

Benign

0.030

.;.;.;.;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.43

T;T;.;T;.;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.13

T;T;T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.36

Sift4G

Benign

0.13

T;T;T;T;T;T

Vest4

0.12

MutPred

0.68

.;.;.;.;.;Gain of disorder (P = 0.011);

MVP

0.095

ClinPred

0.029

GERP RS

-3.6

Varity_R

0.041

gMVP

0.20

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