Variant 6-7884419-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_030810.5(TXNDC5):c.1116G>A(p.Ala372=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,614,088 control chromosomes in the GnomAD database, including 910 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 0.016 ( 151 hom., cov: 32)

Exomes 𝑓: 0.0094 ( 759 hom. )

Consequence

TXNDC5
NM_030810.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.888

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:):

BLOC1S5-TXNDC5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP7

Synonymous conserved (PhyloP=-0.888 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TXNDC5	NM_030810.5 linkuse as main transcript	c.1116G>A	p.Ala372=	synonymous_variant	9/10	ENST00000379757.9
BLOC1S5-TXNDC5	NR_037616.1 linkuse as main transcript	n.1275G>A		non_coding_transcript_exon_variant	12/13
TXNDC5	NM_001145549.4 linkuse as main transcript	c.792G>A	p.Ala264=	synonymous_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNDC5	ENST00000379757.9 linkuse as main transcript	c.1116G>A	p.Ala372=	synonymous_variant	9/10	1	NM_030810.5	P1	Q8NBS9-1
TXNDC5	ENST00000473453.2 linkuse as main transcript	c.792G>A	p.Ala264=	synonymous_variant	9/10	1			Q8NBS9-2
TXNDC5	ENST00000460138.5 linkuse as main transcript	n.894G>A		non_coding_transcript_exon_variant	3/4	2
TXNDC5	ENST00000475802.1 linkuse as main transcript	n.410G>A		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.0160

AC:

2439

AN:

152106

Hom.:

150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00280

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0864

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.00932

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00207

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0312

AC:

7849

AN:

251494

Hom.:

557

AF XY:

0.0261

AC XY:

3551

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.00351

Gnomad AMR exome

AF:

0.133

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.149

Gnomad SAS exome

AF:

0.00431

Gnomad FIN exome

AF:

0.000554

Gnomad NFE exome

AF:

0.00126

Gnomad OTH exome

AF:

0.0249

GnomAD4 exome

AF:

0.00945

AC:

13812

AN:

1461864

Hom.:

759

Cov.:

AF XY:

0.00877

AC XY:

6380

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00206

Gnomad4 AMR exome

AF:

0.129

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.123

Gnomad4 SAS exome

AF:

0.00441

Gnomad4 FIN exome

AF:

0.000449

Gnomad4 NFE exome

AF:

0.00174

Gnomad4 OTH exome

AF:

0.0124

GnomAD4 genome

AF:

0.0161

AC:

2449

AN:

152224

Hom.:

151

Cov.:

AF XY:

0.0183

AC XY:

1364

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00279

Gnomad4 AMR

AF:

0.0868

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.00953

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00207

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.00653

Hom.:

Bravo

AF:

0.0240

Asia WGS

AF:

0.0580

AC:

201

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.00154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

5.6

DANN

Benign

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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