rs368074

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_030810.5(TXNDC5):​c.519+240G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,058 control chromosomes in the GnomAD database, including 7,963 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 0.31 ( 7963 hom., cov: 32)

Consequence

TXNDC5
NM_030810.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.424
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TXNDC5NM_030810.5 linkuse as main transcriptc.519+240G>C intron_variant ENST00000379757.9
BLOC1S5-TXNDC5NR_037616.1 linkuse as main transcriptn.678+240G>C intron_variant, non_coding_transcript_variant
TXNDC5NM_001145549.4 linkuse as main transcriptc.195+240G>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TXNDC5ENST00000379757.9 linkuse as main transcriptc.519+240G>C intron_variant 1 NM_030810.5 P1Q8NBS9-1
TXNDC5ENST00000473453.2 linkuse as main transcriptc.195+240G>C intron_variant 1 Q8NBS9-2
TXNDC5ENST00000469459.1 linkuse as main transcriptn.667+240G>C intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.309
AC:
46889
AN:
151940
Hom.:
7951
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.331
Gnomad AMI
AF:
0.464
Gnomad AMR
AF:
0.434
Gnomad ASJ
AF:
0.206
Gnomad EAS
AF:
0.648
Gnomad SAS
AF:
0.294
Gnomad FIN
AF:
0.253
Gnomad MID
AF:
0.241
Gnomad NFE
AF:
0.254
Gnomad OTH
AF:
0.314
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.309
AC:
46935
AN:
152058
Hom.:
7963
Cov.:
32
AF XY:
0.313
AC XY:
23248
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.331
Gnomad4 AMR
AF:
0.434
Gnomad4 ASJ
AF:
0.206
Gnomad4 EAS
AF:
0.649
Gnomad4 SAS
AF:
0.294
Gnomad4 FIN
AF:
0.253
Gnomad4 NFE
AF:
0.254
Gnomad4 OTH
AF:
0.318
Alfa
AF:
0.271
Hom.:
747
Bravo
AF:
0.328
Asia WGS
AF:
0.456
AC:
1582
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
0.47
DANN
Benign
0.39

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: rs368074; hg19: chr6-7899569; API