rs7746818

chr6-7889233-A-Gchr6-7889233-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030810.5(TXNDC5):c.819+262T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 472,336 control chromosomes in the GnomAD database, including 156 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 (86 hom., cov: 33)
  • Exomes 𝑓: 0.016 (70 hom.)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101

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]

BLOC1S5-TXNDC5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNDC5	NM_030810.5	c.819+262T>C		intron_variant		ENST00000379757.9
BLOC1S5-TXNDC5	NR_037616.1	n.978+262T>C		intron_variant, non_coding_transcript_variant
TXNDC5	NM_001145549.4	c.495+262T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNDC5	ENST00000379757.9	c.819+262T>C		intron_variant		1	NM_030810.5	P1
TXNDC5	ENST00000473453.2	c.495+262T>C		intron_variant		1
TXNDC5	ENST00000460138.5	n.213T>C		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes AF: 0.0281 AC: 4281 AN: 152158 Hom.: 84 Cov.: 33

Gnomad AFR AF: 0.0605

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0240

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.00565

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0173

Gnomad OTH AF: 0.0268

GnomAD4 exome AF: 0.0158 AC: 5061 AN: 320060 Hom.: 70 Cov.: 4 AF XY: 0.0157 AC XY: 2607 AN XY: 165870

Gnomad4 AFR exome AF: 0.0632

Gnomad4 AMR exome AF: 0.0169

Gnomad4 ASJ exome AF: 0.0185

Gnomad4 EAS exome AF: 0.0000413

Gnomad4 SAS exome AF: 0.00659

Gnomad4 FIN exome AF: 0.00861

Gnomad4 NFE exome AF: 0.0168

Gnomad4 OTH exome AF: 0.0180

GnomAD4 genome AF: 0.0282 AC: 4292 AN: 152276 Hom.: 86 Cov.: 33 AF XY: 0.0276 AC XY: 2058 AN XY: 74460

Gnomad4 AFR AF: 0.0605

Gnomad4 AMR AF: 0.0241

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.00565

Gnomad4 NFE AF: 0.0173

Gnomad4 OTH AF: 0.0255

Alfa AF: 0.0208 Hom.: 8

Bravo AF: 0.0302

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.6
Dann	Benign	0.63

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

LitVar

Other links and lift over

dbSNP: rs7746818; hg19: chr6-7889466;