Variant 19-43592100-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001007561.3(IRGQ):c.1798G>A(p.Val600Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

IRGQ
NM_001007561.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

Variant links:

Genes affected

IRGQ (HGNC:24868): (immunity related GTPase Q) Predicted to enable GTP binding activity. [provided by Alliance of Genome Resources, Apr 2022]

IRGQ links:

ENSG00000268361 (HGNC:):

ENSG00000268361 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3009683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRGQ	NM_001007561.3 link	c.1798G>A	p.Val600Ile	missense_variant	3/3	ENST00000422989.6	NP_001007562.1	Q8WZA9
IRGQ	NM_001388309.1 link	c.1798G>A	p.Val600Ile	missense_variant	3/3		NP_001375238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IRGQ	ENST00000422989.6 link	c.1798G>A	p.Val600Ile	missense_variant	3/3	5	NM_001007561.3	ENSP00000387535.1	Q8WZA9
IRGQ	ENST00000602269.2 link	c.1798G>A	p.Val600Ile	missense_variant	2/2	1		ENSP00000472250.1	Q8WZA9
ENSG00000268361	ENST00000594374.1 link	c.168+768G>A		intron_variant		3		ENSP00000472698.1	M0R2N6
IRGQ	ENST00000601520.1 link	n.251+657G>A		intron_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460070

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726364

show subpopulations

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:

0.0000192

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Aug 17, 2022

The c.1798G>A (p.V600I) alteration is located in exon 3 (coding exon 2) of the IRGQ gene. This alteration results from a G to A substitution at nucleotide position 1798, causing the valine (V) at amino acid position 600 to be replaced by an isoleucine (I). 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

0.24

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

T;T

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.59

T;.

M_CAP

Benign

0.016

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

1.6

L;L

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.070

N;.

REVEL

Benign

0.16

Sift

Benign

0.16

T;.

Sift4G

Benign

0.30

T;T

Polyphen

1.0

D;D

Vest4

0.11

MutPred

0.46

Gain of catalytic residue at L605 (P = 0.0317);Gain of catalytic residue at L605 (P = 0.0317);

MVP

0.43

ClinPred

0.67

GERP RS

4.9

Varity_R

0.060

gMVP

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over