NM_030810.5:c.1047-581G>A

Variant names:

• chr6-7885069-C-T
• rs1225937
• NM_030810.5:c.1047-581G>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.1047-581G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,020 control chromosomes in the GnomAD database, including 24,021 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 0.53 (24021 hom., cov: 32)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.580
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC5	NM_030810.5	MANE Select	c.1047-581G>A		intron	N/A	NP_110437.2
	TXNDC5	NM_001145549.4		c.723-581G>A		intron	N/A	NP_001139021.1
	BLOC1S5-TXNDC5	NR_037616.1		n.1206-581G>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.1047-581G>A		intron	N/A	ENSP00000369081.4
	TXNDC5	ENST00000473453.2	TSL:1	c.723-581G>A		intron	N/A	ENSP00000420784.1
	BLOC1S5-TXNDC5	ENST00000439343.2	TSL:2	n.*745-581G>A		intron	N/A	ENSP00000454697.1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80662 AN: 151902 Hom.: 23961 Cov.: 32

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.500

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.531 AC: 80786 AN: 152020 Hom.: 24021 Cov.: 32 AF XY: 0.535 AC XY: 39755 AN XY: 74308

African (AFR) AF: 0.788 AC: 32660 AN: 41452

American (AMR) AF: 0.582 AC: 8893 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1084 AN: 3468

East Asian (EAS) AF: 0.764 AC: 3947 AN: 5168

South Asian (SAS) AF: 0.402 AC: 1934 AN: 4806

European-Finnish (FIN) AF: 0.431 AC: 4547 AN: 10562

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26039 AN: 67966

Other (OTH) AF: 0.506 AC: 1068 AN: 2112

Alfa AF: 0.446 Hom.: 3426

Bravo AF: 0.560

Asia WGS AF: 0.621 AC: 2159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.57
PhyloP100		-0.58
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: rs1225937; hg19: chr6-7885302;