Variant 17-6641093-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032731.4(TXNDC17):c.11A>T(p.Tyr4Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00028 in 1,612,956 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 1 hom. )

Consequence

TXNDC17
NM_032731.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0950

Variant links:

Genes affected

TXNDC17 (HGNC:28218): (thioredoxin domain containing 17) Enables peroxidase activity and protein-disulfide reductase (NAD(P)) activity. Involved in tumor necrosis factor-mediated signaling pathway. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TXNDC17 links:

TXNDC17 (HGNC:):

TXNDC17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038224757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNDC17	NM_032731.4 linkuse as main transcript	c.11A>T	p.Tyr4Phe	missense_variant	1/4	ENST00000250101.10	NP_116120.1	Q9BRA2A0A140VJY7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNDC17	ENST00000250101.10 linkuse as main transcript	c.11A>T	p.Tyr4Phe	missense_variant	1/4	1	NM_032731.4	ENSP00000250101.5		Q9BRA2

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.000529

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000217

AC:

AN:

248680

Hom.:

AF XY:

0.000215

AC XY:

AN XY:

135098

show subpopulations

Gnomad AFR exome

AF:

0.0000629

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000934

Gnomad NFE exome

AF:

0.000411

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000281

AC:

410

AN:

1460774

Hom.:

Cov.:

AF XY:

0.000275

AC XY:

200

AN XY:

726680

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000760

Gnomad4 NFE exome

AF:

0.000344

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000269

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000529

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.000268

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.000474

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

Aug 11, 2022

The c.11A>T (p.Y4F) alteration is located in exon 1 (coding exon 1) of the TXNDC17 gene. This alteration results from a A to T substitution at nucleotide position 11, causing the tyrosine (Y) at amino acid position 4 to be replaced by a phenylalanine (F). 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

0.072

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.0

DANN

Benign

0.61

DEOGEN2

Benign

0.013

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.038

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.69

N;.;.

REVEL

Benign

0.027

Sift

Benign

0.74

T;.;.

Sift4G

Benign

0.78

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.10

MVP

0.32

MPC

0.14

ClinPred

0.015

GERP RS

-2.1

Varity_R

0.24

gMVP

0.52

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