dbSNP rs1225944: TXNDC5:c.820-7T>C (chr6-7888855-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_030810.5(TXNDC5):c.820-7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 1,599,936 control chromosomes in the GnomAD database, including 159,072 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.54 ( 25217 hom., cov: 33)

Exomes 𝑓: 0.42 ( 133855 hom. )

Consequence

TXNDC5
NM_030810.5 splice_region, intron

Scores

Splicing: ADA: 0.00005265

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.506

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TXNDC5	NM_030810.5 link	c.820-7T>C	splice_region_variant, intron_variant	Intron 6 of 9	ENST00000379757.9	NP_110437.2	Q8NBS9-1
TXNDC5	NM_001145549.4 link	c.496-7T>C	splice_region_variant, intron_variant	Intron 6 of 9		NP_001139021.1	Q8NBS9-2A0A024QZV0
BLOC1S5-TXNDC5	NR_037616.1 link	n.979-7T>C	splice_region_variant, intron_variant	Intron 9 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNDC5	ENST00000379757.9 link	c.820-7T>C		splice_region_variant, intron_variant	Intron 6 of 9	1	NM_030810.5	ENSP00000369081.4		Q8NBS9-1
BLOC1S5-TXNDC5	ENST00000439343.2 link	n.*518-7T>C		splice_region_variant, intron_variant	Intron 9 of 12	2		ENSP00000454697.1		H3BN57

Frequencies

GnomAD3 genomes

AF:

0.541

AC:

82239

AN:

152074

Hom.:

25151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.818

Gnomad AMI

AF:

0.544

Gnomad AMR

AF:

0.588

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.764

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.431

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.384

Gnomad OTH

AF:

0.507

GnomAD3 exomes

AF:

0.486

AC:

116413

AN:

239360

Hom.:

31701

AF XY:

0.466

AC XY:

60279

AN XY:

129280

show subpopulations

Gnomad AFR exome

AF:

0.831

Gnomad AMR exome

AF:

0.695

Gnomad ASJ exome

AF:

0.316

Gnomad EAS exome

AF:

0.758

Gnomad SAS exome

AF:

0.399

Gnomad FIN exome

AF:

0.437

Gnomad NFE exome

AF:

0.381

Gnomad OTH exome

AF:

0.425

GnomAD4 exome

AF:

0.416

AC:

601946

AN:

1447744

Hom.:

133855

Cov.:

AF XY:

0.412

AC XY:

296473

AN XY:

719060

show subpopulations

Gnomad4 AFR exome

AF:

0.835

Gnomad4 AMR exome

AF:

0.678

Gnomad4 ASJ exome

AF:

0.316

Gnomad4 EAS exome

AF:

0.781

Gnomad4 SAS exome

AF:

0.400

Gnomad4 FIN exome

AF:

0.425

Gnomad4 NFE exome

AF:

0.382

Gnomad4 OTH exome

AF:

0.441

GnomAD4 genome

AF:

0.541

AC:

82369

AN:

152192

Hom.:

25217

Cov.:

AF XY:

0.544

AC XY:

40492

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.818

Gnomad4 AMR

AF:

0.588

Gnomad4 ASJ

AF:

0.312

Gnomad4 EAS

AF:

0.764

Gnomad4 SAS

AF:

0.410

Gnomad4 FIN

AF:

0.431

Gnomad4 NFE

AF:

0.384

Gnomad4 OTH

AF:

0.512

Alfa

AF:

0.466

Hom.:

8142

Bravo

AF:

0.570

Asia WGS

AF:

0.629

AC:

2186

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.17

DANN

Benign

0.38

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000053

dbscSNV1_RF

Benign

0.058

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over