rs9502656

Positions:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The ENST00000379757.9(TXNDC5):​c.1290C>T​(p.Asp430=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 1,614,084 control chromosomes in the GnomAD database, including 2,118 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.074 ( 1003 hom., cov: 32)
Exomes 𝑓: 0.023 ( 1115 hom. )

Consequence

TXNDC5
ENST00000379757.9 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.768
Variant links:
Genes affected
TXNDC5 (HGNC:21073): (thioredoxin domain containing 5) This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal endoplasmic reticulum (ER)-signal sequence, three catalytically active thioredoxin domains and a C-terminal ER-retention sequence. Its expression is induced by hypoxia and its role may be to protect hypoxic cells from apoptosis. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring upstream BLOC1S5 gene. [provided by RefSeq, Dec 2016]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP7
Synonymous conserved (PhyloP=-0.768 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TXNDC5NM_030810.5 linkuse as main transcriptc.1290C>T p.Asp430= synonymous_variant 10/10 ENST00000379757.9 NP_110437.2
BLOC1S5-TXNDC5NR_037616.1 linkuse as main transcriptn.1449C>T non_coding_transcript_exon_variant 13/13
TXNDC5NM_001145549.4 linkuse as main transcriptc.966C>T p.Asp322= synonymous_variant 10/10 NP_001139021.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TXNDC5ENST00000379757.9 linkuse as main transcriptc.1290C>T p.Asp430= synonymous_variant 10/101 NM_030810.5 ENSP00000369081 P1Q8NBS9-1
TXNDC5ENST00000473453.2 linkuse as main transcriptc.966C>T p.Asp322= synonymous_variant 10/101 ENSP00000420784 Q8NBS9-2
TXNDC5ENST00000460138.5 linkuse as main transcriptn.1068C>T non_coding_transcript_exon_variant 4/42
TXNDC5ENST00000475802.1 linkuse as main transcript downstream_gene_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0736
AC:
11193
AN:
152106
Hom.:
1003
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.214
Gnomad AMI
AF:
0.00219
Gnomad AMR
AF:
0.0467
Gnomad ASJ
AF:
0.0280
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00518
Gnomad FIN
AF:
0.00593
Gnomad MID
AF:
0.0633
Gnomad NFE
AF:
0.0188
Gnomad OTH
AF:
0.0618
GnomAD3 exomes
AF:
0.0295
AC:
7429
AN:
251442
Hom.:
431
AF XY:
0.0252
AC XY:
3423
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.217
Gnomad AMR exome
AF:
0.0258
Gnomad ASJ exome
AF:
0.0266
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00679
Gnomad FIN exome
AF:
0.00688
Gnomad NFE exome
AF:
0.0196
Gnomad OTH exome
AF:
0.0256
GnomAD4 exome
AF:
0.0232
AC:
33843
AN:
1461860
Hom.:
1115
Cov.:
30
AF XY:
0.0222
AC XY:
16137
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.220
Gnomad4 AMR exome
AF:
0.0269
Gnomad4 ASJ exome
AF:
0.0250
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00777
Gnomad4 FIN exome
AF:
0.00753
Gnomad4 NFE exome
AF:
0.0193
Gnomad4 OTH exome
AF:
0.0298
GnomAD4 genome
AF:
0.0736
AC:
11208
AN:
152224
Hom.:
1003
Cov.:
32
AF XY:
0.0723
AC XY:
5381
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.214
Gnomad4 AMR
AF:
0.0466
Gnomad4 ASJ
AF:
0.0280
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00539
Gnomad4 FIN
AF:
0.00593
Gnomad4 NFE
AF:
0.0187
Gnomad4 OTH
AF:
0.0602
Alfa
AF:
0.0458
Hom.:
275
Bravo
AF:
0.0828
Asia WGS
AF:
0.0150
AC:
54
AN:
3478
EpiCase
AF:
0.0218
EpiControl
AF:
0.0220

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
0.29
DANN
Benign
0.82
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs9502656; hg19: chr6-7883386; API