NM_002164.6:c.134A>G

Variant names:

• chr8-39917921-A-G
• rs1807200746
• NM_002164.6:c.134A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002164.6(IDO1):​c.134A>G​(p.His45Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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. H45P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: IDO1 NM_002164.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 0 publications found

Genes affected

IDO1 (HGNC:6059): (indoleamine 2,3-dioxygenase 1) This gene encodes indoleamine 2,3-dioxygenase (IDO) - a heme enzyme that catalyzes the first and rate-limiting step in tryptophan catabolism to N-formyl-kynurenine. This enzyme acts on multiple tryptophan substrates including D-tryptophan, L-tryptophan, 5-hydroxy-tryptophan, tryptamine, and serotonin. This enzyme is thought to play a role in a variety of pathophysiological processes such as antimicrobial and antitumor defense, neuropathology, immunoregulation, and antioxidant activity. Through its expression in dendritic cells, monocytes, and macrophages this enzyme modulates T-cell behavior by its peri-cellular catabolization of the essential amino acid tryptophan.[provided by RefSeq, Feb 2011]

ENSG00000253939 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20312688).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002164.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDO1	NM_002164.6	MANE Select	c.134A>G	p.His45Arg	missense	Exon 2 of 10	NP_002155.1	P14902

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IDO1	ENST00000518237.6	TSL:1 MANE Select	c.134A>G	p.His45Arg	missense	Exon 2 of 10	ENSP00000430950.1	P14902
	IDO1	ENST00000522495.5	TSL:5	c.134A>G	p.His45Arg	missense	Exon 4 of 12	ENSP00000430505.1	P14902
	IDO1	ENST00000519154.5	TSL:5	c.134A>G	p.His45Arg	missense	Exon 3 of 7	ENSP00000428716.1	A0A140T9Z2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461156 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726928

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53236

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111528

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.4
DANN	Benign	0.71
DEOGEN2	Benign	0.0098	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.060	N
PhyloP100		2.0
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.12
Sift	Benign	0.30	T
Sift4G	Uncertain	0.025	D
Polyphen		0.25	B
Vest4		0.086
MutPred		0.58		Loss of ubiquitination at K44 (P = 0.0516)
MVP		0.22
MPC		0.040
ClinPred		0.49	T
GERP RS		5.6
Varity_R		0.25
gMVP		0.24
Mutation Taster		=95/5	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: rs1807200746; hg19: chr8-39775440;