19-43592442-G-C

Variant names:

• chr19-43592442-G-C
• rs1370611758
• NM_001007561.3:c.1456C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001007561.3(IRGQ):​c.1456C>G​(p.Leu486Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000253 in 1,583,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: IRGQ NM_001007561.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.104
• Publications: 0 publications found

Genes affected

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

ENSG00000268361 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29669917).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRGQ	NM_001007561.3	c.1456C>G	p.Leu486Val	missense_variant	Exon 3 of 3	ENST00000422989.6	NP_001007562.1
IRGQ	NM_001388309.1	c.1456C>G	p.Leu486Val	missense_variant	Exon 3 of 3		NP_001375238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRGQ	ENST00000422989.6	c.1456C>G	p.Leu486Val	missense_variant	Exon 3 of 3	5	NM_001007561.3	ENSP00000387535.1
IRGQ	ENST00000602269.2	c.1456C>G	p.Leu486Val	missense_variant	Exon 2 of 2	1		ENSP00000472250.1
ENSG00000268361	ENST00000594374.1	c.168+426C>G		intron_variant	Intron 1 of 2	3		ENSP00000472698.1
IRGQ	ENST00000601520.1	n.251+315C>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1431120 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 711214

African (AFR) AF: 0.0000607 AC: 2 AN: 32948

American (AMR) AF: 0.00 AC: 0 AN: 42864

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25764

East Asian (EAS) AF: 0.00 AC: 0 AN: 38626

South Asian (SAS) AF: 0.00 AC: 0 AN: 84742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5376

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104536

Other (OTH) AF: 0.0000168 AC: 1 AN: 59402

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152214 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74348

African (AFR) AF: 0.0000241 AC: 1 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1456C>G (p.L486V) alteration is located in exon 3 (coding exon 2) of the IRGQ gene. This alteration results from a C to G substitution at nucleotide position 1456, causing the leucine (L) at amino acid position 486 to be replaced by a valine (V). 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	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.60	T;.
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.6	L;L
PhyloP100		-0.10
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.2	N;.
REVEL	Benign	0.19
Sift	Uncertain	0.011	D;.
Sift4G	Benign	0.40	T;T
Polyphen		1.0	D;D
Vest4		0.23
MutPred		0.45		Loss of stability (P = 0.0748);Loss of stability (P = 0.0748);
MVP		0.50
ClinPred		0.49	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.092
gMVP		0.48
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1370611758; hg19: chr19-44096594;