6-7894561-G-T

Variant names:

• chr6-7894561-G-T
• rs1238994
• NM_030810.5:c.616+545C>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.616+545C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,968 control chromosomes in the GnomAD database, including 12,189 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 0.37 (12189 hom., cov: 32)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515
• 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 (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNDC5	NM_030810.5	c.616+545C>A		intron_variant	Intron 4 of 9	ENST00000379757.9	NP_110437.2
TXNDC5	NM_001145549.4	c.292+545C>A		intron_variant	Intron 4 of 9		NP_001139021.1
BLOC1S5-TXNDC5	NR_037616.1	n.775+545C>A		intron_variant	Intron 7 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNDC5	ENST00000379757.9	c.616+545C>A		intron_variant	Intron 4 of 9	1	NM_030810.5	ENSP00000369081.4
TXNDC5	ENST00000473453.2	c.292+545C>A		intron_variant	Intron 4 of 9	1		ENSP00000420784.1
BLOC1S5-TXNDC5	ENST00000439343.2	n.*314+545C>A		intron_variant	Intron 7 of 12	2		ENSP00000454697.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56863 AN: 151850 Hom.: 12163 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.375 AC: 56944 AN: 151968 Hom.: 12189 Cov.: 32 AF XY: 0.377 AC XY: 27993 AN XY: 74268

African (AFR) AF: 0.545 AC: 22584 AN: 41442

American (AMR) AF: 0.465 AC: 7095 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 702 AN: 3470

East Asian (EAS) AF: 0.646 AC: 3346 AN: 5176

South Asian (SAS) AF: 0.290 AC: 1397 AN: 4816

European-Finnish (FIN) AF: 0.258 AC: 2718 AN: 10550

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17831 AN: 67946

Other (OTH) AF: 0.364 AC: 769 AN: 2114

Alfa AF: 0.315 Hom.: 1076

Bravo AF: 0.401

Asia WGS AF: 0.473 AC: 1644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.46
PhyloP100		-0.52
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: rs1238994; hg19: chr6-7894794;