rs35871461
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_030810.5(TXNDC5):c.1176+301G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 152,306 control chromosomes in the GnomAD database, including 15 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 0.012 ( 15 hom., cov: 32)
Consequence
TXNDC5
NM_030810.5 intron
NM_030810.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.410
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 -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0123 (1875/152306) while in subpopulation NFE AF= 0.0171 (1164/68022). AF 95% confidence interval is 0.0163. There are 15 homozygotes in gnomad4. There are 898 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 15 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TXNDC5 | NM_030810.5 | c.1176+301G>A | intron_variant | ENST00000379757.9 | |||
BLOC1S5-TXNDC5 | NR_037616.1 | n.1335+301G>A | intron_variant, non_coding_transcript_variant | ||||
TXNDC5 | NM_001145549.4 | c.852+301G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TXNDC5 | ENST00000379757.9 | c.1176+301G>A | intron_variant | 1 | NM_030810.5 | P1 | |||
TXNDC5 | ENST00000473453.2 | c.852+301G>A | intron_variant | 1 | |||||
TXNDC5 | ENST00000460138.5 | n.954+301G>A | intron_variant, non_coding_transcript_variant | 2 | |||||
TXNDC5 | ENST00000475802.1 | n.470+301G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0123 AC: 1874AN: 152188Hom.: 15 Cov.: 32
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? AF: 0.0123 AC: 1875AN: 152306Hom.: 15 Cov.: 32 AF XY: 0.0121 AC XY: 898AN XY: 74474
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?
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3478
ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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