Genetic Variant TXNDC2:p.Pro167Thr (chr18-9887179-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The NM_032243.6(TXNDC2):c.499C>A(p.Pro167Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00395 in 1,585,672 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0041 ( 18 hom. )

Consequence

TXNDC2
NM_032243.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.51

Variant links:

Genes affected

TXNDC2 (HGNC:16470): (thioredoxin domain containing 2) Enables thioredoxin-disulfide reductase activity. Predicted to be involved in cell differentiation and cellular oxidant detoxification. Predicted to act upstream of or within cellular response to reactive oxygen species and flagellated sperm motility. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TXNDC2 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=0.004492551).

BP6

Variant 18-9887179-C-A is Benign according to our data. Variant chr18-9887179-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648567.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNDC2	NM_032243.6 link	c.499C>A	p.Pro167Thr	missense_variant	Exon 2 of 2	ENST00000357775.6	NP_115619.4	Q86VQ3-2
TXNDC2	NM_001098529.2 link	c.700C>A	p.Pro234Thr	missense_variant	Exon 2 of 2		NP_001091999.1	Q86VQ3-1A0A140VJY8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNDC2	ENST00000357775.6 link	c.499C>A	p.Pro167Thr	missense_variant	Exon 2 of 2	1	NM_032243.6	ENSP00000350419.4		Q86VQ3-2

Frequencies

GnomAD3 genomes

AF:

0.00284

AC:

428

AN:

150538

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000417

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000792

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00455

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00509

Gnomad OTH

AF:

0.00195

GnomAD3 exomes

AF:

0.00354

AC:

889

AN:

251340

Hom.:

AF XY:

0.00339

AC XY:

461

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00439

Gnomad NFE exome

AF:

0.00659

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.00407

AC:

5843

AN:

1435032

Hom.:

Cov.:

136

AF XY:

0.00396

AC XY:

2824

AN XY:

713824

show subpopulations

Gnomad4 AFR exome

AF:

0.000516

Gnomad4 AMR exome

AF:

0.000276

Gnomad4 ASJ exome

AF:

0.000728

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00463

Gnomad4 NFE exome

AF:

0.00492

Gnomad4 OTH exome

AF:

0.00288

GnomAD4 genome

AF:

0.00284

AC:

428

AN:

150640

Hom.:

Cov.:

AF XY:

0.00284

AC XY:

209

AN XY:

73560

show subpopulations

Gnomad4 AFR

AF:

0.000416

Gnomad4 AMR

AF:

0.000791

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00455

Gnomad4 NFE

AF:

0.00509

Gnomad4 OTH

AF:

0.00193

Alfa

AF:

0.00438

Hom.:

Bravo

AF:

0.00241

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00441

AC:

535

EpiCase

AF:

0.00420

EpiControl

AF:

0.00409

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TXNDC2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.21

DANN

Benign

0.94

DEOGEN2

Benign

0.062

.;.;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.32

T;T;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.0045

T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Uncertain

2.3

M;.;M

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.4

.;N;N

REVEL

Benign

0.079

Sift

Benign

0.047

.;D;D

Sift4G

Benign

0.089

T;T;T

Polyphen

0.95

.;.;P

Vest4

0.061

MVP

0.55

MPC

0.054

ClinPred

0.027

GERP RS

0.57

Varity_R

0.046

gMVP

0.064

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