rs1208538553

Variant names:

• chr19-43592100-C-G
• rs1208538553
• NM_001007561.3:c.1798G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-43592100-C-G
• chr19-43592100-C-T

Variant summary

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

The NM_001007561.3(IRGQ):​c.1798G>C​(p.Val600Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V600I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IRGQ NM_001007561.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• 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=0.34433833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRGQ	NM_001007561.3	c.1798G>C	p.Val600Leu	missense_variant	Exon 3 of 3	ENST00000422989.6	NP_001007562.1
IRGQ	NM_001388309.1	c.1798G>C	p.Val600Leu	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.1798G>C	p.Val600Leu	missense_variant	Exon 3 of 3	5	NM_001007561.3	ENSP00000387535.1
IRGQ	ENST00000602269.2	c.1798G>C	p.Val600Leu	missense_variant	Exon 2 of 2	1		ENSP00000472250.1
ENSG00000268361	ENST00000594374.1	c.168+768G>C		intron_variant	Intron 1 of 2	3		ENSP00000472698.1
IRGQ	ENST00000601520.1	n.251+657G>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0037	T;T
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.61	T;.
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.6	L;L
PhyloP100		1.1
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.44	N;.
REVEL	Benign	0.21
Sift	Benign	0.19	T;.
Sift4G	Benign	0.28	T;T
Polyphen		1.0	D;D
Vest4		0.30
MutPred		0.52		Gain of disorder (P = 0.1266);Gain of disorder (P = 0.1266);
MVP		0.60
ClinPred		0.68	D
GERP RS		4.9
Varity_R		0.085
gMVP		0.38
Mutation Taster		=88/12	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: rs1208538553; hg19: chr19-44096252;