6-7898642-A-G

Variant names:

• chr6-7898642-A-G
• rs369086
• NM_030810.5:c.519+934T>C

Variant summary

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

The NM_030810.5(TXNDC5):​c.519+934T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 151,882 control chromosomes in the GnomAD database, including 23,586 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 (23586 hom., cov: 31)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 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.519+934T>C		intron	N/A	NP_110437.2
	TXNDC5	NM_001145549.4		c.195+934T>C		intron	N/A	NP_001139021.1
	BLOC1S5-TXNDC5	NR_037616.1		n.678+934T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC5	ENST00000379757.9	TSL:1 MANE Select	c.519+934T>C		intron	N/A	ENSP00000369081.4
	TXNDC5	ENST00000473453.2	TSL:1	c.195+934T>C		intron	N/A	ENSP00000420784.1
	BLOC1S5-TXNDC5	ENST00000439343.2	TSL:2	n.*217+934T>C		intron	N/A	ENSP00000454697.1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79690 AN: 151764 Hom.: 23531 Cov.: 31

Gnomad AFR AF: 0.784

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.525 AC: 79808 AN: 151882 Hom.: 23586 Cov.: 31 AF XY: 0.530 AC XY: 39330 AN XY: 74252

African (AFR) AF: 0.784 AC: 32453 AN: 41400

American (AMR) AF: 0.578 AC: 8832 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1053 AN: 3466

East Asian (EAS) AF: 0.762 AC: 3921 AN: 5148

South Asian (SAS) AF: 0.407 AC: 1959 AN: 4812

European-Finnish (FIN) AF: 0.430 AC: 4536 AN: 10542

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25398 AN: 67930

Other (OTH) AF: 0.497 AC: 1047 AN: 2106

Alfa AF: 0.421 Hom.: 24194

Bravo AF: 0.553

Asia WGS AF: 0.621 AC: 2156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.2
DANN	Benign	0.31
PhyloP100		0.041
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: rs369086; hg19: chr6-7898875;