8-39913932-G-T

Variant names:

• chr8-39913932-G-T
• rs35059413
• NM_002164.6:c.10G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002164.6(IDO1):​c.10G>T​(p.Ala4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,890 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. A4T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: IDO1 NM_002164.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 7 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060528696).

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.10G>T	p.Ala4Ser	missense	Exon 1 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.10G>T	p.Ala4Ser	missense	Exon 1 of 10	ENSP00000430950.1	P14902
	IDO1	ENST00000522495.5	TSL:5	c.10G>T	p.Ala4Ser	missense	Exon 3 of 12	ENSP00000430505.1	P14902
	IDO1	ENST00000519154.5	TSL:5	c.10G>T	p.Ala4Ser	missense	Exon 2 of 7	ENSP00000428716.1	A0A140T9Z2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416890 Hom.: 0 Cov.: 29 AF XY: 0.00000143 AC XY: 1 AN XY: 700418

African (AFR) AF: 0.0000309 AC: 1 AN: 32336

American (AMR) AF: 0.00 AC: 0 AN: 37452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25364

East Asian (EAS) AF: 0.00 AC: 0 AN: 37412

South Asian (SAS) AF: 0.00 AC: 0 AN: 80106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50742

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1088824

Other (OTH) AF: 0.00 AC: 0 AN: 58942

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 15

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.051
DANN	Benign	0.72
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.21
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.015
Sift	Benign	0.93	T
Sift4G	Benign	0.63	T
Polyphen		0.66	P
Vest4		0.060
MutPred		0.22		Gain of loop (P = 0.024)
MVP		0.21
MPC		0.035
ClinPred		0.12	T
GERP RS		-0.40
PromoterAI		-0.12	Neutral
Varity_R		0.043
gMVP		0.31
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs35059413; hg19: chr8-39771451;