chr19-43592885-G-T

Position:

• chr19-43592885-G-T

Variant summary

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

The NM_001007561.3(IRGQ):​c.1013C>A​(p.Pro338Gln) variant causes a missense 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. 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)
• Consequence: IRGQ NM_001007561.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3264297).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRGQ	NM_001007561.3	c.1013C>A	p.Pro338Gln	missense_variant	3/3	ENST00000422989.6	NP_001007562.1
IRGQ	NM_001388309.1	c.1013C>A	p.Pro338Gln	missense_variant	3/3		NP_001375238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRGQ	ENST00000422989.6	c.1013C>A	p.Pro338Gln	missense_variant	3/3	5	NM_001007561.3	ENSP00000387535.1
IRGQ	ENST00000602269.2	c.1013C>A	p.Pro338Gln	missense_variant	2/2	1		ENSP00000472250.1
ENSG00000268361	ENST00000594374.1	c.151C>A	p.Arg51Arg	synonymous_variant	1/3	3		ENSP00000472698.1
IRGQ	ENST00000601520.1	n.123C>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Jun 16, 2024

The c.1013C>A (p.P338Q) alteration is located in exon 3 (coding exon 2) of the IRGQ gene. This alteration results from a C to A substitution at nucleotide position 1013, causing the proline (P) at amino acid position 338 to be replaced by a glutamine (Q). 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	0.33
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.032	T;T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.52	T;.
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.5	M;M
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.66	N;.
REVEL	Benign	0.19
Sift	Benign	0.089	T;.
Sift4G	Uncertain	0.017	D;D
Polyphen		0.99	D;D
Vest4		0.40
MutPred		0.24		Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);
MVP		0.87
ClinPred		0.91	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.062
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr19-44097037;