chr18-9886925-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000357775.6(TXNDC2):ā€‹c.245T>Cā€‹(p.Ile82Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 30)
Exomes š‘“: 0.0000014 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TXNDC2
ENST00000357775.6 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.37
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 -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.034422636).
BP6
Variant 18-9886925-T-C is Benign according to our data. Variant chr18-9886925-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2533947.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TXNDC2NM_032243.6 linkuse as main transcriptc.245T>C p.Ile82Thr missense_variant 2/2 ENST00000357775.6 NP_115619.4 Q86VQ3-2
TXNDC2NM_001098529.2 linkuse as main transcriptc.446T>C p.Ile149Thr missense_variant 2/2 NP_001091999.1 Q86VQ3-1A0A140VJY8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TXNDC2ENST00000357775.6 linkuse as main transcriptc.245T>C p.Ile82Thr missense_variant 2/21 NM_032243.6 ENSP00000350419.4 Q86VQ3-2

Frequencies

GnomAD3 genomes
AF:
0.00000664
AC:
1
AN:
150636
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000148
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460496
Hom.:
0
Cov.:
115
AF XY:
0.00
AC XY:
0
AN XY:
726592
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000664
AC:
1
AN:
150636
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
73462
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000148
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsApr 06, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
0.043
DANN
Benign
0.97
DEOGEN2
Benign
0.0046
.;T;T;.;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.013
N
LIST_S2
Benign
0.37
T;T;T;T;T
M_CAP
Benign
0.0022
T
MetaRNN
Benign
0.034
T;T;T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.68
N;.;.;.;N
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
0.46
.;N;.;N;N
REVEL
Benign
0.0030
Sift
Benign
0.63
.;T;.;T;T
Sift4G
Benign
0.87
T;T;T;T;T
Polyphen
0.11
.;.;.;.;B
Vest4
0.052
MutPred
0.26
Gain of phosphorylation at I149 (P = 0.0046);.;.;.;Gain of phosphorylation at I149 (P = 0.0046);
MVP
0.13
MPC
0.079
ClinPred
0.084
T
GERP RS
0.14
Varity_R
0.025
gMVP
0.0094

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: rs1477949684; hg19: chr18-9886922; API