Genetic Variant TXNDC5:c.1176+301G>A (chr6-7884058-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.410

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:

Genome browser will be placed here

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=-0.85).

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TXNDC5	NM_030810.5 link	c.1176+301G>A	intron_variant	Intron 9 of 9	ENST00000379757.9	NP_110437.2	Q8NBS9-1
TXNDC5	NM_001145549.4 link	c.852+301G>A	intron_variant	Intron 9 of 9		NP_001139021.1	Q8NBS9-2A0A024QZV0
BLOC1S5-TXNDC5	NR_037616.1 link	n.1335+301G>A	intron_variant	Intron 12 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNDC5	ENST00000379757.9 link	c.1176+301G>A		intron_variant	Intron 9 of 9	1	NM_030810.5	ENSP00000369081.4		Q8NBS9-1
BLOC1S5-TXNDC5	ENST00000439343.2 link	n.*874+301G>A		intron_variant	Intron 12 of 12	2		ENSP00000454697.1		H3BN57

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1874

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00589

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0169

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.00565

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0171

Gnomad OTH

AF:

0.0163

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

GnomAD4 genome

AF:

0.0123

AC:

1875

AN:

152306

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

898

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00589

AC:

245

AN:

41574

American (AMR)

AF:

0.0169

AC:

258

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0222

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00497

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00565

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0171

AC:

1164

AN:

68022

Other (OTH)

AF:

0.0151

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

174

261

348

435

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0125

Hom.:

Bravo

AF:

0.0128

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.4

(source)

DANN

Benign

0.65

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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