Variant 17-6641173-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_032731.4(TXNDC17):c.91T>C(p.Phe31Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TXNDC17
NM_032731.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.15

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.955

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNDC17	NM_032731.4 linkuse as main transcript	c.91T>C	p.Phe31Leu	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.91T>C	p.Phe31Leu	missense_variant	1/4	1	NM_032731.4	ENSP00000250101.5		Q9BRA2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250718

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461440

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

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

Nov 20, 2024

The c.91T>C (p.F31L) alteration is located in exon 1 (coding exon 1) of the TXNDC17 gene. This alteration results from a T to C substitution at nucleotide position 91, causing the phenylalanine (F) at amino acid position 31 to be replaced by a leucine (L). 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

Pathogenic

0.96

BayesDel_addAF

Uncertain

0.087

BayesDel_noAF

Uncertain

-0.030

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

T;T

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.053

MetaRNN

Pathogenic

0.95

D;D

MetaSVM

Uncertain

-0.24

MutationAssessor

Pathogenic

3.1

M;.

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-5.4

D;.

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.029

D;D

Polyphen

1.0

D;.

Vest4

0.78

MutPred

0.87

Loss of methylation at K35 (P = 0.08);Loss of methylation at K35 (P = 0.08);

MVP

0.78

MPC

0.72

ClinPred

1.0

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.97

gMVP

0.88

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