dbSNP rs34963444: TXNDC5:c.732+470A>G (chr6-7891151-T-C) – 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.732+470A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0278 in 152,296 control chromosomes in the GnomAD database, including 83 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 0.028 ( 83 hom., cov: 33)

Consequence

TXNDC5
NM_030810.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.408

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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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=-0.69).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
TXNDC5	NM_030810.5 link	c.732+470A>G	intron_variant	Intron 5 of 9	ENST00000379757.9	NP_110437.2
TXNDC5	NM_001145549.4 link	c.408+470A>G	intron_variant	Intron 5 of 9		NP_001139021.1
BLOC1S5-TXNDC5	NR_037616.1 link	n.891+470A>G	intron_variant	Intron 8 of 12

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
TXNDC5	ENST00000379757.9 link	c.732+470A>G	intron_variant	Intron 5 of 9	1	NM_030810.5	ENSP00000369081.4
TXNDC5	ENST00000473453.2 link	c.408+470A>G	intron_variant	Intron 5 of 9	1		ENSP00000420784.1
BLOC1S5-TXNDC5	ENST00000439343.2 link	n.*430+470A>G	intron_variant	Intron 8 of 12	2		ENSP00000454697.1

Frequencies

GnomAD3 genomes

AF:

0.0278

AC:

4233

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0602

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0237

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.00565

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0169

Gnomad OTH

AF:

0.0259

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

GnomAD4 genome

AF:

0.0278

AC:

4240

AN:

152296

Hom.:

Cov.:

AF XY:

0.0275

AC XY:

2045

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0601

AC:

2499

AN:

41550

American (AMR)

AF:

0.0237

AC:

363

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0222

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00477

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00565

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0169

AC:

1151

AN:

68032

Other (OTH)

AF:

0.0246

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

210

421

631

842

1052

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0223

Hom.:

Bravo

AF:

0.0299

Asia WGS

AF:

0.00520

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

0.41

Mutation Taster

=100/0

polymorphism

(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