6-7887935-C-T

Variant names:

• chr6-7887935-C-T
• rs89715
• NM_030810.5:c.963+770G>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.963+770G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,960 control chromosomes in the GnomAD database, including 10,596 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 0.36 (10596 hom., cov: 32)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 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.963+770G>A		intron	N/A	NP_110437.2
	TXNDC5	NM_001145549.4		c.639+770G>A		intron	N/A	NP_001139021.1
	BLOC1S5-TXNDC5	NR_037616.1		n.1122+770G>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.963+770G>A		intron	N/A	ENSP00000369081.4
	TXNDC5	ENST00000473453.2	TSL:1	c.639+770G>A		intron	N/A	ENSP00000420784.1
	BLOC1S5-TXNDC5	ENST00000439343.2	TSL:2	n.*661+770G>A		intron	N/A	ENSP00000454697.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54035 AN: 151842 Hom.: 10570 Cov.: 32

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.356 AC: 54110 AN: 151960 Hom.: 10596 Cov.: 32 AF XY: 0.358 AC XY: 26585 AN XY: 74266

African (AFR) AF: 0.465 AC: 19264 AN: 41420

American (AMR) AF: 0.457 AC: 6977 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 749 AN: 3466

East Asian (EAS) AF: 0.646 AC: 3332 AN: 5156

South Asian (SAS) AF: 0.294 AC: 1415 AN: 4808

European-Finnish (FIN) AF: 0.258 AC: 2728 AN: 10580

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18399 AN: 67940

Other (OTH) AF: 0.355 AC: 749 AN: 2110

Alfa AF: 0.335 Hom.: 1640

Bravo AF: 0.379

Asia WGS AF: 0.471 AC: 1638 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.66
PhyloP100		-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: rs89715; hg19: chr6-7888168;