19-43592264-G-C

Position:

• chr19-43592264-G-C

Variant summary

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

The NM_001007561.3(IRGQ):​c.1634C>G​(p.Ala545Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,423,138 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: IRGQ NM_001007561.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.13

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

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=0.12114337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRGQ	NM_001007561.3	c.1634C>G	p.Ala545Gly	missense_variant	3/3	ENST00000422989.6	NP_001007562.1
IRGQ	NM_001388309.1	c.1634C>G	p.Ala545Gly	missense_variant	3/3		NP_001375238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRGQ	ENST00000422989.6	c.1634C>G	p.Ala545Gly	missense_variant	3/3	5	NM_001007561.3	ENSP00000387535.1
IRGQ	ENST00000602269.2	c.1634C>G	p.Ala545Gly	missense_variant	2/2	1		ENSP00000472250.1
ENSG00000268361	ENST00000594374.1	c.168+604C>G		intron_variant		3		ENSP00000472698.1
IRGQ	ENST00000601520.1	n.251+493C>G		intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1423138 Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1 AN XY: 706814

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000266

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000169

GnomAD4 genome Cov.: 33

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

Dec 22, 2023

The c.1634C>G (p.A545G) 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 1634, causing the alanine (A) at amino acid position 545 to be replaced by a glycine (G). 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	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.032	T;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.54	T;.
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.7	N;.
REVEL	Benign	0.10
Sift	Benign	0.065	T;.
Sift4G	Benign	0.24	T;T
Polyphen		0.45	B;B
Vest4		0.12
MutPred		0.31		Loss of stability (P = 0.0251);Loss of stability (P = 0.0251);
MVP		0.47
ClinPred		0.25	T
GERP RS		3.9
Varity_R		0.17
gMVP		0.52

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: chr19-44096416;