6-7909734-C-T

Position:

• chr6-7909734-C-T

Variant summary

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

The NM_030810.5(TXNDC5):​c.263+780G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 980,718 control chromosomes in the GnomAD database, including 107,357 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 0.39 (12521 hom., cov: 32)
  • Exomes 𝑓: 0.48 (94836 hom.)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNDC5	NM_030810.5	c.263+780G>A		intron_variant		ENST00000379757.9
BLOC1S5-TXNDC5	NR_037616.1	n.423-5011G>A		intron_variant, non_coding_transcript_variant
TXNDC5	NM_001145549.4	c.-62+79G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNDC5	ENST00000379757.9	c.263+780G>A		intron_variant		1	NM_030810.5	P1
TXNDC5	ENST00000473453.2	c.-62+79G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.388 AC: 59003 AN: 151894 Hom.: 12524 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.476 AC: 394332 AN: 828704 Hom.: 94836 AF XY: 0.477 AC XY: 182783 AN XY: 382958

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.354

Gnomad4 ASJ exome AF: 0.549

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.459

Gnomad4 FIN exome AF: 0.517

Gnomad4 NFE exome AF: 0.483

Gnomad4 OTH exome AF: 0.453

GnomAD4 genome AF: 0.388 AC: 59004 AN: 152014 Hom.: 12521 Cov.: 32 AF XY: 0.385 AC XY: 28633 AN XY: 74326

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.562

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.407

Alfa AF: 0.446 Hom.: 3129

Bravo AF: 0.369

Asia WGS AF: 0.302 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs13209404; hg19: chr6-7909967;