rs45441296
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_030810.5(TXNDC5):c.868G>A(p.Val290Met) variant causes a missense change. The variant allele was found at a frequency of 0.000173 in 1,614,120 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00018 ( 0 hom. )
Consequence
TXNDC5
NM_030810.5 missense
NM_030810.5 missense
Scores
9
10
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.28
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3301196).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TXNDC5 | NM_030810.5 | c.868G>A | p.Val290Met | missense_variant | 7/10 | ENST00000379757.9 | NP_110437.2 | |
BLOC1S5-TXNDC5 | NR_037616.1 | n.1027G>A | non_coding_transcript_exon_variant | 10/13 | ||||
TXNDC5 | NM_001145549.4 | c.544G>A | p.Val182Met | missense_variant | 7/10 | NP_001139021.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TXNDC5 | ENST00000379757.9 | c.868G>A | p.Val290Met | missense_variant | 7/10 | 1 | NM_030810.5 | ENSP00000369081 | P1 | |
TXNDC5 | ENST00000473453.2 | c.544G>A | p.Val182Met | missense_variant | 7/10 | 1 | ENSP00000420784 | |||
TXNDC5 | ENST00000460138.5 | n.646G>A | non_coding_transcript_exon_variant | 1/4 | 2 | |||||
TXNDC5 | ENST00000475802.1 | n.162G>A | non_coding_transcript_exon_variant | 1/4 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152230Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000119 AC: 30AN: 251122Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135700
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GnomAD4 exome AF: 0.000175 AC: 256AN: 1461772Hom.: 0 Cov.: 31 AF XY: 0.000158 AC XY: 115AN XY: 727176
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GnomAD4 genome AF: 0.000158 AC: 24AN: 152348Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74496
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at