17-6642259-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032731.4(TXNDC17):ā€‹c.238C>Gā€‹(p.Pro80Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000553 in 1,609,558 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000085 ( 0 hom., cov: 33)
Exomes š‘“: 0.000052 ( 0 hom. )

Consequence

TXNDC17
NM_032731.4 missense

Scores

1
8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.46
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TXNDC17NM_032731.4 linkc.238C>G p.Pro80Ala missense_variant 3/4 ENST00000250101.10 NP_116120.1 Q9BRA2A0A140VJY7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TXNDC17ENST00000250101.10 linkc.238C>G p.Pro80Ala missense_variant 3/41 NM_032731.4 ENSP00000250101.5 Q9BRA2

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152172
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
248508
Hom.:
0
AF XY:
0.0000149
AC XY:
2
AN XY:
134348
show subpopulations
Gnomad AFR exome
AF:
0.0000621
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:
0.0000266
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000521
AC:
76
AN:
1457386
Hom.:
0
Cov.:
29
AF XY:
0.0000428
AC XY:
31
AN XY:
724966
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.00
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:
0.0000658
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152172
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000113
Hom.:
0
Bravo
AF:
0.0000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsDec 13, 2022The c.238C>G (p.P80A) alteration is located in exon 3 (coding exon 3) of the TXNDC17 gene. This alteration results from a C to G substitution at nucleotide position 238, causing the proline (P) at amino acid position 80 to be replaced by an alanine (A). 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
0.087
BayesDel_addAF
Benign
-0.049
T
BayesDel_noAF
Benign
-0.13
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.15
T;T
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.86
D;D
M_CAP
Benign
0.0079
T
MetaRNN
Uncertain
0.61
D;D
MetaSVM
Benign
-0.62
T
MutationAssessor
Uncertain
2.7
M;.
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-3.6
D;.
REVEL
Uncertain
0.50
Sift
Benign
0.25
T;.
Sift4G
Benign
0.19
T;T
Polyphen
0.62
P;.
Vest4
0.63
MVP
0.65
MPC
0.36
ClinPred
0.54
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.53
gMVP
0.48

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.

Other links and lift over

dbSNP: rs368381490; hg19: chr17-6545579; API