Genetic Variant NM_001007561.3:c.1850C>T (chr19-43592048-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001007561.3(IRGQ):c.1850C>T(p.Ala617Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,804 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: 0.0000021 ( 0 hom. )

Consequence

IRGQ
NM_001007561.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

Publications

0 publications found

Variant links:

Genes affected

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

IRGQ links:

ENSG00000268361 (HGNC:):

ENSG00000268361 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRGQ	NM_001007561.3 link	c.1850C>T	p.Ala617Val	missense_variant	Exon 3 of 3	ENST00000422989.6	NP_001007562.1	Q8WZA9
IRGQ	NM_001388309.1 link	c.1850C>T	p.Ala617Val	missense_variant	Exon 3 of 3		NP_001375238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IRGQ	ENST00000422989.6 link	c.1850C>T	p.Ala617Val	missense_variant	Exon 3 of 3	5	NM_001007561.3	ENSP00000387535.1	Q8WZA9
IRGQ	ENST00000602269.2 link	c.1850C>T	p.Ala617Val	missense_variant	Exon 2 of 2	1		ENSP00000472250.1	Q8WZA9
ENSG00000268361	ENST00000594374.1 link	c.168+820C>T		intron_variant	Intron 1 of 2	3		ENSP00000472698.1	M0R2N6
IRGQ	ENST00000601520.1 link	n.251+709C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1454804

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722890

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33396

American (AMR)

AF:

0.00

AC:

AN:

44352

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25738

East Asian (EAS)

AF:

0.00

AC:

AN:

39546

South Asian (SAS)

AF:

0.00

AC:

AN:

85646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1108026

Other (OTH)

AF:

0.0000167

AC:

AN:

60050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 10, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1850C>T (p.A617V) alteration is located in exon 3 (coding exon 2) of the IRGQ gene. This alteration results from a C to T substitution at nucleotide position 1850, causing the alanine (A) at amino acid position 617 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

0.15

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.54

T;.

M_CAP

Benign

0.0094

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

PhyloP100

1.6

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.72

N;.

REVEL

Benign

0.052

Sift

Benign

0.15

T;.

Sift4G

Uncertain

0.024

D;D

Polyphen

0.91

P;P

Vest4

0.14

MutPred

0.24

Loss of disorder (P = 0.062);Loss of disorder (P = 0.062);

MVP

0.51

ClinPred

0.57

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.035

gMVP

0.25

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.36

Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_001007561.3:c.1850C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over