6-7909734-C-T

Variant names:

• chr6-7909734-C-T
• rs13209404
• NM_030810.5:c.263+780G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000379757.9(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 ENST00000379757.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770
• Publications: 7 publications found

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: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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000379757.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC5	NM_030810.5	MANE Select	c.263+780G>A		intron	N/A	NP_110437.2
	TXNDC5	NM_001145549.4		c.-62+79G>A		intron	N/A	NP_001139021.1
	BLOC1S5-TXNDC5	NR_037616.1		n.423-5011G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC5	ENST00000379757.9	TSL:1 MANE Select	c.263+780G>A		intron	N/A	ENSP00000369081.4
	TXNDC5	ENST00000473453.2	TSL:1	c.-62+79G>A		intron	N/A	ENSP00000420784.1
	BLOC1S5-TXNDC5	ENST00000439343.2	TSL:2	n.373-5011G>A		intron	N/A	ENSP00000454697.1

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

African (AFR) AF: 0.216 AC: 3380 AN: 15674

American (AMR) AF: 0.354 AC: 346 AN: 978

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 2822 AN: 5142

East Asian (EAS) AF: 0.221 AC: 797 AN: 3606

South Asian (SAS) AF: 0.459 AC: 7525 AN: 16378

European-Finnish (FIN) AF: 0.517 AC: 302 AN: 584

Middle Eastern (MID) AF: 0.478 AC: 773 AN: 1616

European-Non Finnish (NFE) AF: 0.483 AC: 366089 AN: 757586

Other (OTH) AF: 0.453 AC: 12298 AN: 27140

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

African (AFR) AF: 0.228 AC: 9478 AN: 41506

American (AMR) AF: 0.349 AC: 5335 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1948 AN: 3464

East Asian (EAS) AF: 0.206 AC: 1060 AN: 5156

South Asian (SAS) AF: 0.440 AC: 2120 AN: 4816

European-Finnish (FIN) AF: 0.466 AC: 4926 AN: 10570

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32757 AN: 67908

Other (OTH) AF: 0.407 AC: 858 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.76
PhyloP100		-0.77
PromoterAI		0.0018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13209404; hg19: chr6-7909967;