chr19-43593092-C-G

Position:

• chr19-43593092-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001007561.3(IRGQ):​c.806G>C​(p.Arg269Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: IRGQ NM_001007561.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27

Genes affected

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

ACMG classification

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=0.29809654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRGQ	NM_001007561.3	c.806G>C	p.Arg269Pro	missense_variant	3/3	ENST00000422989.6	NP_001007562.1
IRGQ	NM_001388309.1	c.806G>C	p.Arg269Pro	missense_variant	3/3		NP_001375238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRGQ	ENST00000422989.6	c.806G>C	p.Arg269Pro	missense_variant	3/3	5	NM_001007561.3	ENSP00000387535.1
IRGQ	ENST00000602269.2	c.806G>C	p.Arg269Pro	missense_variant	2/2	1		ENSP00000472250.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434434 Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1 AN XY: 709170

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: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Apr 19, 2024

The c.806G>C (p.R269P) alteration is located in exon 3 (coding exon 2) of the IRGQ gene. This alteration results from a G to C substitution at nucleotide position 806, causing the arginine (R) at amino acid position 269 to be replaced by a proline (P). 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	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.045	T;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.76	T;.
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.9	N;.
REVEL	Benign	0.15
Sift	Benign	0.20	T;.
Sift4G	Benign	0.30	T;T
Polyphen		1.0	D;D
Vest4		0.36
MutPred		0.40		Gain of glycosylation at R269 (P = 0.0279);Gain of glycosylation at R269 (P = 0.0279);
MVP		0.81
ClinPred		0.95	D
GERP RS		4.5
Varity_R		0.48
gMVP		0.94

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: chr19-44097244;