1-27666428-C-T

Variant names:

• chr1-27666428-C-T
• NM_002038.4:c.346G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002038.4(IFI6):​c.346G>A​(p.Gly116Ser) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: IFI6 NM_002038.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.11

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.934

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFI6	NM_002038.4	c.346G>A	p.Gly116Ser	missense_variant	Exon 5 of 5	ENST00000361157.11	NP_002029.3
IFI6	NM_022873.3	c.370G>A	p.Gly124Ser	missense_variant	Exon 5 of 5		NP_075011.1
IFI6	NM_022872.3	c.358G>A	p.Gly120Ser	missense_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.346G>A	p.Gly116Ser	missense_variant	Exon 5 of 5	1	NM_002038.4	ENSP00000354736.6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.370G>A (p.G124S) 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 370, causing the glycine (G) at amino acid position 124 to be replaced by a serine (S). 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	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T;.;.
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.93	D;D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Pathogenic	3.1	M;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.5	D;D;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.027	D;D;D
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.78
MutPred		0.75		Gain of catalytic residue at G116 (P = 0.0506);.;.;
MVP		0.59
MPC		1.7
ClinPred		0.98	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.90

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: chr1-27992939;