rs34782746

Variant names:

• chr6-7889021-C-T
• rs34782746
• NM_030810.5:c.820-173G>A

Variant summary

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

The NM_030810.5(TXNDC5):​c.820-173G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 814,662 control chromosomes in the GnomAD database, including 209 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 (84 hom., cov: 33)
  • Exomes 𝑓: 0.016 (125 hom.)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0585 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030810.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC5	NM_030810.5	MANE Select	c.820-173G>A		intron	N/A	NP_110437.2
	TXNDC5	NM_001145549.4		c.496-173G>A		intron	N/A	NP_001139021.1	Q8NBS9-2
	BLOC1S5-TXNDC5	NR_037616.1		n.979-173G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC5	ENST00000379757.9	TSL:1 MANE Select	c.820-173G>A		intron	N/A	ENSP00000369081.4	Q8NBS9-1
	TXNDC5	ENST00000473453.2	TSL:1	c.496-173G>A		intron	N/A	ENSP00000420784.1	Q8NBS9-2
	BLOC1S5-TXNDC5	ENST00000439343.2	TSL:2	n.*518-173G>A		intron	N/A	ENSP00000454697.1	H3BN57

Frequencies

GnomAD3 genomes AF: 0.0281 AC: 4279 AN: 152152 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: 0.00476

Gnomad FIN AF: 0.00565

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0173

Gnomad OTH AF: 0.0263

GnomAD4 exome AF: 0.0158 AC: 10495 AN: 662392 Hom.: 125 Cov.: 9 AF XY: 0.0157 AC XY: 5254 AN XY: 335158

African (AFR) AF: 0.0594 AC: 857 AN: 14436

American (AMR) AF: 0.0155 AC: 216 AN: 13948

Ashkenazi Jewish (ASJ) AF: 0.0191 AC: 273 AN: 14322

East Asian (EAS) AF: 0.0000354 AC: 1 AN: 28262

South Asian (SAS) AF: 0.00709 AC: 304 AN: 42874

European-Finnish (FIN) AF: 0.00840 AC: 247 AN: 29396

Middle Eastern (MID) AF: 0.0224 AC: 71 AN: 3164

European-Non Finnish (NFE) AF: 0.0164 AC: 7941 AN: 483370

Other (OTH) AF: 0.0179 AC: 585 AN: 32620

GnomAD4 genome AF: 0.0281 AC: 4286 AN: 152270 Hom.: 84 Cov.: 33 AF XY: 0.0276 AC XY: 2058 AN XY: 74448

African (AFR) AF: 0.0605 AC: 2512 AN: 41530

American (AMR) AF: 0.0240 AC: 368 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4826

European-Finnish (FIN) AF: 0.00565 AC: 60 AN: 10612

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0173 AC: 1177 AN: 68024

Other (OTH) AF: 0.0251 AC: 53 AN: 2112

Alfa AF: 0.0221 Hom.: 10

Bravo AF: 0.0301

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.18
DANN	Benign	0.73
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism

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: rs34782746; hg19: chr6-7889254;