6-7882840-C-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000439343.2(BLOC1S5-TXNDC5):​n.*1301G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BLOC1S5-TXNDC5 ENST00000439343.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.677
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNDC5	NM_030810.5	c.*304G>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000379757.9	NP_110437.2
BLOC1S5-TXNDC5	NR_037616.1	n.1762G>T		non_coding_transcript_exon_variant	Exon 13 of 13
TXNDC5	NM_001145549.4	c.*304G>T		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>T		non_coding_transcript_exon_variant	Exon 13 of 13	2		ENSP00000454697.1
TXNDC5	ENST00000379757.9	c.*304G>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_030810.5	ENSP00000369081.4
BLOC1S5-TXNDC5	ENST00000439343.2	n.*1301G>T		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000454697.1
TXNDC5	ENST00000460138.5	n.1381G>T		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 88792 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 45688

African (AFR) AF: 0.00 AC: 0 AN: 3360

American (AMR) AF: 0.00 AC: 0 AN: 4516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3036

East Asian (EAS) AF: 0.00 AC: 0 AN: 6406

South Asian (SAS) AF: 0.00 AC: 0 AN: 5878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 376

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 56434

Other (OTH) AF: 0.00 AC: 0 AN: 5360

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		0.68

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;