Variant 1-27666473-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000361157.11(IFI6):c.301G>A(p.Ala101Thr) variant causes a missense, splice region 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. 12/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

IFI6
ENST00000361157.11 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0530

Variant links:

Genes affected

IFI6 (HGNC:4054): (interferon alpha inducible protein 6) This gene was first identified as one of the many genes induced by interferon. The encoded protein may play a critical role in the regulation of apoptosis. A minisatellite that consists of 26 repeats of a 12 nucleotide repeating element resembling the mammalian splice donor consensus sequence begins near the end of the second exon. Alternatively spliced transcript variants that encode different isoforms by using the two downstream repeat units as splice donor sites have been described. [provided by RefSeq, Jul 2008]

IFI6 links:

Genome browser will be placed here

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=0.19311711).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IFI6	NM_002038.4 linkuse as main transcript	c.301G>A	p.Ala101Thr	missense_variant, splice_region_variant	5/5	ENST00000361157.11	NP_002029.3
IFI6	NM_022873.3 linkuse as main transcript	c.325G>A	p.Ala109Thr	missense_variant, splice_region_variant	5/5		NP_075011.1
IFI6	NM_022872.3 linkuse as main transcript	c.313G>A	p.Ala105Thr	missense_variant, splice_region_variant	5/5		NP_075010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFI6	ENST00000361157.11 linkuse as main transcript	c.301G>A	p.Ala101Thr	missense_variant, splice_region_variant	5/5	1	NM_002038.4	ENSP00000354736	A2	P09912-1
IFI6	ENST00000362020.4 linkuse as main transcript	c.313G>A	p.Ala105Thr	missense_variant, splice_region_variant	5/5	1		ENSP00000355152	P4	P09912-2
IFI6	ENST00000339145.8 linkuse as main transcript	c.325G>A	p.Ala109Thr	missense_variant, splice_region_variant	5/5	2		ENSP00000342513	A2	P09912-3
IFI6	ENST00000679644.1 linkuse as main transcript	c.301G>A	p.Ala101Thr	missense_variant, splice_region_variant	5/5			ENSP00000505325	A2	P09912-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460708

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726746

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 16, 2023

The c.325G>A (p.A109T) alteration is located in exon 5 (coding exon 4) of the IFI6 gene. This alteration results from a G to A substitution at nucleotide position 325, causing the alanine (A) at amino acid position 109 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

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.22

T;.;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.84

T;T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

M;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Benign

0.036

Sift

Benign

0.060

T;D;D

Sift4G

Benign

0.14

T;T;T

Polyphen

0.043

B;B;.

Vest4

0.15

MutPred

0.68

Gain of loop (P = 0.1069);.;.;

MVP

0.16

MPC

0.70

ClinPred

0.36

GERP RS

0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.10

gMVP

0.60

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over