19-18175041-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006332.5(IFI30):c.134C>A(p.Thr45Lys) 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. 17/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: IFI30 NM_006332.5 missense, splice_region
• Scores: Splicing: ADA: 0.003350
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.991

Genes affected

IFI30 (HGNC:5398): (IFI30 lysosomal thiol reductase) The protein encoded by this gene is a lysosomal thiol reductase that at low pH can reduce protein disulfide bonds. The enzyme is expressed constitutively in antigen-presenting cells and induced by gamma-interferon in other cell types. This enzyme has an important role in MHC class II-restricted antigen processing. [provided by RefSeq, Jul 2008]

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=0.08898744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFI30	NM_006332.5	c.134C>A	p.Thr45Lys	missense_variant, splice_region_variant	2/7	ENST00000407280.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFI30	ENST00000407280.4	c.134C>A	p.Thr45Lys	missense_variant, splice_region_variant	2/7	1	NM_006332.5	P1
IFI30	ENST00000597802.2	c.134C>A	p.Thr45Lys	missense_variant, splice_region_variant	3/3	3
IFI30	ENST00000600463.1	n.873C>A		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2023

The c.134C>A (p.T45K) alteration is located in exon 2 (coding exon 2) of the IFI30 gene. This alteration results from a C to A substitution at nucleotide position 134, causing the threonine (T) at amino acid position 45 to be replaced by a lysine (K). 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	0.086
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	0.21
Dann	Benign	0.73
DEOGEN2	Benign	0.011	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.35	T;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.089	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.29	T
Sift4G	Benign	0.092	T;T
Polyphen		0.023	.;B
Vest4		0.12
MutPred		0.56		Gain of solvent accessibility (P = 0.0328);Gain of solvent accessibility (P = 0.0328);
MVP		0.19
MPC		0.021
ClinPred		0.066	T
GERP RS		-5.8
Varity_R		0.058
gMVP		0.66

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0034
dbscSNV1_RF	Benign	0.33
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: chr19-18285851;