Variant 4-155908938-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005651.4(TDO2):c.355T>C(p.Ser119Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00046 in 1,613,256 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00046 ( 5 hom. )

Consequence

TDO2
NM_005651.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.70

Variant links:

Genes affected

TDO2 (HGNC:11708): (tryptophan 2,3-dioxygenase) This gene encodes a heme enzyme that plays a critical role in tryptophan metabolism by catalyzing the first and rate-limiting step of the kynurenine pathway. Increased activity of the encoded protein and subsequent kynurenine production may also play a role in cancer through the suppression of antitumor immune responses, and single nucleotide polymorphisms in this gene may be associated with autism. [provided by RefSeq, Feb 2012]

TDO2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008334935).

BP6

Variant 4-155908938-T-C is Benign according to our data. Variant chr4-155908938-T-C is described in ClinVar as [Benign]. Clinvar id is 783385.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 63 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TDO2	NM_005651.4 linkuse as main transcript	c.355T>C	p.Ser119Pro	missense_variant	5/12	ENST00000536354.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TDO2	ENST00000536354.3 linkuse as main transcript	c.355T>C	p.Ser119Pro	missense_variant	5/12	1	NM_005651.4	P1
TDO2	ENST00000512584.5 linkuse as main transcript	n.2025T>C		non_coding_transcript_exon_variant	2/9	1
TDO2	ENST00000506072.5 linkuse as main transcript	c.34T>C	p.Ser12Pro	missense_variant	7/8	3
TDO2	ENST00000507590.5 linkuse as main transcript	c.34T>C	p.Ser12Pro	missense_variant	6/7	4

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00232

AC:

582

AN:

250342

Hom.:

AF XY:

0.00157

AC XY:

213

AN XY:

135314

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0167

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00197

GnomAD4 exome

AF:

0.000465

AC:

679

AN:

1461068

Hom.:

Cov.:

AF XY:

0.000347

AC XY:

252

AN XY:

726800

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0148

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.000414

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000195

Hom.:

Bravo

AF:

0.00119

ExAC

AF:

0.00183

AC:

222

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

Cadd

Benign

Dann

Benign

0.90

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.26

MetaRNN

Benign

0.0083

T;T;T

MetaSVM

Benign

-0.71

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.23

Sift

Benign

0.054

T;D;D

Sift4G

Benign

0.29

T;T;T

Polyphen

0.029

.;.;B

Vest4

0.63

MutPred

0.60

.;.;Loss of MoRF binding (P = 0.0574);

MVP

0.072

MPC

0.058

ClinPred

0.068

GERP RS

-4.0

Varity_R

0.41

gMVP

0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over