Variant 17-6641101-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_032731.4(TXNDC17):c.19G>A(p.Val7Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00772 in 1,613,456 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0079 ( 85 hom. )

Consequence

TXNDC17
NM_032731.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.94

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035151541).

BP6

Variant 17-6641101-G-A is Benign according to our data. Variant chr17-6641101-G-A is described in ClinVar as [Benign]. Clinvar id is 774345.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNDC17	NM_032731.4 linkuse as main transcript	c.19G>A	p.Val7Met	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.19G>A	p.Val7Met	missense_variant	1/4	1	NM_032731.4	ENSP00000250101.5		Q9BRA2

Frequencies

GnomAD3 genomes

AF:

0.00615

AC:

936

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00850

Gnomad ASJ

AF:

0.0444

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00579

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00775

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00736

AC:

1836

AN:

249558

Hom.:

AF XY:

0.00724

AC XY:

980

AN XY:

135422

show subpopulations

Gnomad AFR exome

AF:

0.00125

Gnomad AMR exome

AF:

0.00594

Gnomad ASJ exome

AF:

0.0496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00477

Gnomad FIN exome

AF:

0.00121

Gnomad NFE exome

AF:

0.00774

Gnomad OTH exome

AF:

0.0118

GnomAD4 exome

AF:

0.00788

AC:

11514

AN:

1461086

Hom.:

Cov.:

AF XY:

0.00774

AC XY:

5625

AN XY:

726836

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.00633

Gnomad4 ASJ exome

AF:

0.0450

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00529

Gnomad4 FIN exome

AF:

0.00135

Gnomad4 NFE exome

AF:

0.00787

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.00614

AC:

935

AN:

152370

Hom.:

Cov.:

AF XY:

0.00553

AC XY:

412

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.00161

Gnomad4 AMR

AF:

0.00849

Gnomad4 ASJ

AF:

0.0444

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00579

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.00775

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00937

Hom.:

Bravo

AF:

0.00659

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.0109

AC:

ExAC

AF:

0.00716

AC:

869

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

T;T;T

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.82

T;T;T

MetaRNN

Benign

0.0035

T;T;T

MetaSVM

Benign

-0.34

MutationAssessor

Pathogenic

2.9

M;.;.

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.73

N;.;.

REVEL

Benign

0.13

Sift

Uncertain

0.0050

D;.;.

Sift4G

Uncertain

0.028

D;T;D

Polyphen

0.95

P;.;.

Vest4

0.41

MVP

0.56

MPC

0.25

ClinPred

0.074

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.37

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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