Variant 18-9886978-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_032243.6(TXNDC2):c.298G>A(p.Ala100Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000095 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TXNDC2
NM_032243.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.20

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021117687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNDC2	NM_032243.6 link	c.298G>A	p.Ala100Thr	missense_variant	2/2	ENST00000357775.6	NP_115619.4	Q86VQ3-2
TXNDC2	NM_001098529.2 link	c.499G>A	p.Ala167Thr	missense_variant	2/2		NP_001091999.1	Q86VQ3-1A0A140VJY8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNDC2	ENST00000357775.6 link	c.298G>A	p.Ala100Thr	missense_variant	2/2	1	NM_032243.6	ENSP00000350419.4		Q86VQ3-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

235

AN:

101738

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00211

Gnomad AMI

AF:

0.00309

Gnomad AMR

AF:

0.00201

Gnomad ASJ

AF:

0.00121

Gnomad EAS

AF:

0.00107

Gnomad SAS

AF:

0.00908

Gnomad FIN

AF:

0.00167

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00229

Gnomad OTH

AF:

0.00274

GnomAD3 exomes

AF:

0.0000463

AC:

AN:

237700

Hom.:

AF XY:

0.0000542

AC XY:

AN XY:

129204

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000100

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000953

AC:

138

AN:

1448408

Hom.:

Cov.:

118

AF XY:

0.0000847

AC XY:

AN XY:

720564

show subpopulations

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:

0.0000355

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000115

Gnomad4 OTH exome

AF:

0.000134

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00232

AC:

236

AN:

101820

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

122

AN XY:

49628

show subpopulations

Gnomad4 AFR

AF:

0.00210

Gnomad4 AMR

AF:

0.00201

Gnomad4 ASJ

AF:

0.00121

Gnomad4 EAS

AF:

0.00107

Gnomad4 SAS

AF:

0.00947

Gnomad4 FIN

AF:

0.00167

Gnomad4 NFE

AF:

0.00229

Gnomad4 OTH

AF:

0.00270

Alfa

AF:

0.00154

Hom.:

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.499G>A (p.A167T) alteration is located in exon 2 (coding exon 2) of the TXNDC2 gene. This alteration results from a G to A substitution at nucleotide position 499, causing the alanine (A) at amino acid position 167 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.050

DANN

Benign

0.79

DEOGEN2

Benign

0.0087

.;T;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0088

LIST_S2

Benign

0.27

T;T;T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.021

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

L;.;.;L

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.52

.;.;N;N

REVEL

Benign

0.0010

Sift

Benign

0.046

.;.;D;T

Sift4G

Benign

0.45

T;T;T;T

Polyphen

0.010

.;.;.;B

Vest4

0.048

MutPred

0.21

Gain of phosphorylation at A167 (P = 0.023);.;.;Gain of phosphorylation at A167 (P = 0.023);

MVP

0.10

MPC

0.049

ClinPred

0.046

GERP RS

-4.1

Varity_R

0.030

gMVP

0.014

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