1-27666473-C-T

Variant summary

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

The NM_002038.4(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
NM_002038.4 missense, splice_region

Scores

3
16

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]
LINC02574 (HGNC:53746): (long intergenic non-protein coding RNA 2574)

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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=0.19311711).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IFI6NM_002038.4 linkc.301G>A p.Ala101Thr missense_variant, splice_region_variant Exon 5 of 5 ENST00000361157.11 NP_002029.3 P09912-1A0A348GSI1
IFI6NM_022873.3 linkc.325G>A p.Ala109Thr missense_variant, splice_region_variant Exon 5 of 5 NP_075011.1 P09912-3
IFI6NM_022872.3 linkc.313G>A p.Ala105Thr missense_variant, splice_region_variant Exon 5 of 5 NP_075010.1 P09912-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IFI6ENST00000361157.11 linkc.301G>A p.Ala101Thr missense_variant, splice_region_variant Exon 5 of 5 1 NM_002038.4 ENSP00000354736.6 P09912-1

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1460708
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
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.:
30

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 16, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
13
DANN
Uncertain
0.97
DEOGEN2
Benign
0.22
T;.;.
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.17
N
LIST_S2
Benign
0.84
T;T;T
M_CAP
Benign
0.0038
T
MetaRNN
Benign
0.19
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;.;.
PrimateAI
Benign
0.42
T
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
T
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.

Other links and lift over

hg19: chr1-27992984; API