dbSNP rs1225937: TXNDC5:c.1047-581G>A (chr6-7885069-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_030810.5(TXNDC5):c.1047-581G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,020 control chromosomes in the GnomAD database, including 24,021 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 0.53 ( 24021 hom., cov: 32)

Consequence

TXNDC5
NM_030810.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.580

Publications

3 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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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 (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
TXNDC5	NM_030810.5 link	c.1047-581G>A	intron_variant	Intron 8 of 9	ENST00000379757.9	NP_110437.2
TXNDC5	NM_001145549.4 link	c.723-581G>A	intron_variant	Intron 8 of 9		NP_001139021.1
BLOC1S5-TXNDC5	NR_037616.1 link	n.1206-581G>A	intron_variant	Intron 11 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNDC5	ENST00000379757.9 link	c.1047-581G>A		intron_variant	Intron 8 of 9	1	NM_030810.5	ENSP00000369081.4
BLOC1S5-TXNDC5	ENST00000439343.2 link	n.*745-581G>A		intron_variant	Intron 11 of 12	2		ENSP00000454697.1

Frequencies

GnomAD3 genomes

AF:

0.531

AC:

80662

AN:

151902

Hom.:

23961

Cov.:

show subpopulations

Gnomad AFR

AF:

0.787

Gnomad AMI

AF:

0.542

Gnomad AMR

AF:

0.582

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.764

Gnomad SAS

AF:

0.403

Gnomad FIN

AF:

0.431

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.383

Gnomad OTH

AF:

0.500

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

GnomAD4 genome

AF:

0.531

AC:

80786

AN:

152020

Hom.:

24021

Cov.:

AF XY:

0.535

AC XY:

39755

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.788

AC:

32660

AN:

41452

American (AMR)

AF:

0.582

AC:

8893

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

1084

AN:

3468

East Asian (EAS)

AF:

0.764

AC:

3947

AN:

5168

South Asian (SAS)

AF:

0.402

AC:

1934

AN:

4806

European-Finnish (FIN)

AF:

0.431

AC:

4547

AN:

10562

Middle Eastern (MID)

AF:

0.412

AC:

121

AN:

294

European-Non Finnish (NFE)

AF:

0.383

AC:

26039

AN:

67966

Other (OTH)

AF:

0.506

AC:

1068

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1692

3384

5075

6767

8459

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

664

1328

1992

2656

3320

<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:

0.446

Hom.:

3426

Bravo

AF:

0.560

Asia WGS

AF:

0.621

AC:

2159

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.0

(source)

DANN

Benign

0.57

PhyloP100

-0.58

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over