18-9886934-C-T

Variant summary

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

The NM_032243.6(TXNDC2):​c.254C>T​(p.Ser85Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 30)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TXNDC2
NM_032243.6 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.565
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]

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=0.04722485).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TXNDC2NM_032243.6 linkc.254C>T p.Ser85Phe missense_variant Exon 2 of 2 ENST00000357775.6 NP_115619.4 Q86VQ3-2
TXNDC2NM_001098529.2 linkc.455C>T p.Ser152Phe missense_variant Exon 2 of 2 NP_001091999.1 Q86VQ3-1A0A140VJY8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TXNDC2ENST00000357775.6 linkc.254C>T p.Ser85Phe missense_variant Exon 2 of 2 1 NM_032243.6 ENSP00000350419.4 Q86VQ3-2

Frequencies

GnomAD3 genomes
AF:
0.0000461
AC:
7
AN:
151848
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000242
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:
0.0000735
Gnomad OTH
AF:
0.000478
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461502
Hom.:
0
Cov.:
116
AF XY:
0.00
AC XY:
0
AN XY:
727058
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000461
AC:
7
AN:
151848
Hom.:
0
Cov.:
30
AF XY:
0.0000539
AC XY:
4
AN XY:
74144
show subpopulations
Gnomad4 AFR
AF:
0.0000242
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:
0.0000735
Gnomad4 OTH
AF:
0.000478
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 05, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.455C>T (p.S152F) alteration is located in exon 2 (coding exon 2) of the TXNDC2 gene. This alteration results from a C to T substitution at nucleotide position 455, causing the serine (S) at amino acid position 152 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
0.14
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
6.2
DANN
Uncertain
0.99
DEOGEN2
Benign
0.094
.;T;.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.021
N
LIST_S2
Benign
0.55
T;T;T;T
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.047
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M;.;.;M
PrimateAI
Benign
0.21
T
PROVEAN
Benign
-1.9
.;N;N;N
REVEL
Benign
0.0040
Sift
Benign
0.32
.;T;T;T
Sift4G
Benign
0.15
T;D;T;T
Polyphen
0.055
.;.;.;B
Vest4
0.11
MVP
0.17
MPC
0.075
ClinPred
0.14
T
GERP RS
-2.0
Varity_R
0.048
gMVP
0.018

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: rs369907879; hg19: chr18-9886931; API