dbSNP rs420970: TXNDC5:c.519+158C>T (chr6-7899418-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_030810.5(TXNDC5):c.519+158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,684 control chromosomes in the GnomAD database, including 19,967 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 0.49 ( 19967 hom., cov: 31)

Consequence

TXNDC5
NM_030810.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.210

Publications

1 publications found

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]

TXNDC5 links:

BLOC1S5-TXNDC5 (HGNC:42001): (BLOC1S5-TXNDC5 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring MUTED (muted homolog) and TXNDC5 (thioredoxin domain containing 5) genes on chromosome 6. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

BLOC1S5-TXNDC5 links:

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new If you want to explore the variant's impact on the transcript NM_030810.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030810.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TXNDC5	NM_030810.5	MANE Select	c.519+158C>T	intron	N/A	NP_110437.2
TXNDC5	NM_001145549.4		c.195+158C>T	intron	N/A	NP_001139021.1	Q8NBS9-2
BLOC1S5-TXNDC5	NR_037616.1		n.678+158C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TXNDC5	ENST00000379757.9	TSL:1 MANE Select	c.519+158C>T	intron	N/A	ENSP00000369081.4	Q8NBS9-1
TXNDC5	ENST00000473453.2	TSL:1	c.195+158C>T	intron	N/A	ENSP00000420784.1	Q8NBS9-2
BLOC1S5-TXNDC5	ENST00000439343.2	TSL:2	n.*217+158C>T	intron	N/A	ENSP00000454697.1	H3BN57

Frequencies

GnomAD3 genomes

AF:

0.488

AC:

74004

AN:

151566

Hom.:

19922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.694

Gnomad AMI

AF:

0.538

Gnomad AMR

AF:

0.550

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.762

Gnomad SAS

AF:

0.403

Gnomad FIN

AF:

0.423

Gnomad MID

AF:

0.355

Gnomad NFE

AF:

0.356

Gnomad OTH

AF:

0.457

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.489

AC:

74111

AN:

151684

Hom.:

19967

Cov.:

AF XY:

0.494

AC XY:

36611

AN XY:

74108

show subpopulations

African (AFR)

AF:

0.694

AC:

28697

AN:

41326

American (AMR)

AF:

0.550

AC:

8394

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

971

AN:

3462

East Asian (EAS)

AF:

0.763

AC:

3927

AN:

5150

South Asian (SAS)

AF:

0.402

AC:

1935

AN:

4812

European-Finnish (FIN)

AF:

0.423

AC:

4439

AN:

10484

Middle Eastern (MID)

AF:

0.358

AC:

103

AN:

288

European-Non Finnish (NFE)

AF:

0.356

AC:

24181

AN:

67900

Other (OTH)

AF:

0.463

AC:

977

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1765

3530

5294

7059

8824

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.439

Hom.:

2074

Bravo

AF:

0.514

Asia WGS

AF:

0.613

AC:

2129

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.8

(source)

DANN

Benign

0.28

PhyloP100

0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over