6-7882840-C-T

Variant names:

• chr6-7882840-C-T
• rs8643
• ENST00000439343.2:n.*1301G>A

Variant summary

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

The ENST00000439343.2(BLOC1S5-TXNDC5):​n.*1301G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 240,798 control chromosomes in the GnomAD database, including 1,098 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 0.092 (695 hom., cov: 32)
  • Exomes 𝑓: 0.091 (403 hom.)
• Consequence: BLOC1S5-TXNDC5 ENST00000439343.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.677
• Publications: 20 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNDC5	NM_030810.5	c.*304G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000379757.9	NP_110437.2
BLOC1S5-TXNDC5	NR_037616.1	n.1762G>A		non_coding_transcript_exon_variant	Exon 13 of 13
TXNDC5	NM_001145549.4	c.*304G>A		3_prime_UTR_variant	Exon 10 of 10		NP_001139021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLOC1S5-TXNDC5	ENST00000439343.2	n.*1301G>A		non_coding_transcript_exon_variant	Exon 13 of 13	2		ENSP00000454697.1
TXNDC5	ENST00000379757.9	c.*304G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_030810.5	ENSP00000369081.4
BLOC1S5-TXNDC5	ENST00000439343.2	n.*1301G>A		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000454697.1
TXNDC5	ENST00000460138.5	n.1381G>A		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 13976 AN: 152032 Hom.: 690 Cov.: 32

Gnomad AFR AF: 0.0736

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0939

Gnomad OTH AF: 0.0869

GnomAD4 exome AF: 0.0911 AC: 8075 AN: 88648 Hom.: 403 Cov.: 3 AF XY: 0.0890 AC XY: 4060 AN XY: 45618

African (AFR) AF: 0.0719 AC: 241 AN: 3352

American (AMR) AF: 0.0972 AC: 438 AN: 4508

Ashkenazi Jewish (ASJ) AF: 0.0618 AC: 187 AN: 3028

East Asian (EAS) AF: 0.0856 AC: 547 AN: 6390

South Asian (SAS) AF: 0.106 AC: 623 AN: 5866

European-Finnish (FIN) AF: 0.143 AC: 489 AN: 3412

Middle Eastern (MID) AF: 0.0984 AC: 37 AN: 376

European-Non Finnish (NFE) AF: 0.0893 AC: 5032 AN: 56366

Other (OTH) AF: 0.0899 AC: 481 AN: 5350

GnomAD4 genome AF: 0.0920 AC: 13996 AN: 152150 Hom.: 695 Cov.: 32 AF XY: 0.0952 AC XY: 7079 AN XY: 74370

African (AFR) AF: 0.0737 AC: 3062 AN: 41524

American (AMR) AF: 0.0770 AC: 1178 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0686 AC: 238 AN: 3470

East Asian (EAS) AF: 0.112 AC: 582 AN: 5176

South Asian (SAS) AF: 0.105 AC: 507 AN: 4814

European-Finnish (FIN) AF: 0.166 AC: 1757 AN: 10564

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0939 AC: 6384 AN: 67996

Other (OTH) AF: 0.0907 AC: 191 AN: 2106

Alfa AF: 0.0913 Hom.: 1255

Bravo AF: 0.0861

Asia WGS AF: 0.133 AC: 460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		0.68
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: rs8643; hg19: chr6-7883073;