1-27666473-C-T

Variant names:

• chr1-27666473-C-T
• NM_002038.4:c.301G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0530

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)

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=0.19311711).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFI6	NM_002038.4	c.301G>A	p.Ala101Thr	missense_variant, splice_region_variant	Exon 5 of 5	ENST00000361157.11	NP_002029.3
IFI6	NM_022873.3	c.325G>A	p.Ala109Thr	missense_variant, splice_region_variant	Exon 5 of 5		NP_075011.1
IFI6	NM_022872.3	c.313G>A	p.Ala105Thr	missense_variant, splice_region_variant	Exon 5 of 5		NP_075010.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFI6	ENST00000361157.11	c.301G>A	p.Ala101Thr	missense_variant, splice_region_variant	Exon 5 of 5	1	NM_002038.4	ENSP00000354736.6

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

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;