rs758635688

Variant names:

• chr5-150848422-C-A
• NM_001145805.2:c.299C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-150848422-C-A
• chr5-150848422-C-T

Variant summary

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

The NM_001145805.2(IRGM):​c.299C>A​(p.Thr100Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,399,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000093 (0 hom.)
• Consequence: IRGM NM_001145805.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

Genes affected

IRGM (HGNC:29597): (immunity related GTPase M) This gene encodes a member of the p47 immunity-related GTPase family. The encoded protein may play a role in the innate immune response by regulating autophagy formation in response to intracellular pathogens. Polymorphisms that affect the normal expression of this gene are associated with a susceptibility to Crohn's disease and tuberculosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2016]

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=0.078243315).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001145805.2	c.299C>A	p.Thr100Asn	missense_variant	Exon 2 of 2	ENST00000522154.2	NP_001139277.1
IRGM	NM_001346557.2	c.299C>A	p.Thr100Asn	missense_variant	Exon 2 of 4		NP_001333486.1
IRGM	NR_170598.1	n.1414C>A		non_coding_transcript_exon_variant	Exon 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154.2	c.299C>A	p.Thr100Asn	missense_variant	Exon 2 of 2	1	NM_001145805.2	ENSP00000428220.1
IRGM	ENST00000520549.1	n.-77C>A		upstream_gene_variant		1		ENSP00000429819.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000929 AC: 13 AN: 1399520 Hom.: 0 Cov.: 32 AF XY: 0.0000116 AC XY: 8 AN XY: 690274

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000120

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.20
DANN	Benign	0.33
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0038	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.0020
Sift	Benign	0.13	T
Sift4G	Benign	0.17	T
Polyphen		0.051	B
Vest4		0.074
MutPred		0.37		Loss of catalytic residue at T100 (P = 0.0654);
MVP		0.014
ClinPred		0.067	T
GERP RS		-6.8
Varity_R		0.053
gMVP		0.076

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: chr5-150227984;