rs8643

Variant names:

• chr6-7882840-C-A
• rs8643
• NM_030810.5:c.*304G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-7882840-C-A
• chr6-7882840-C-G
• chr6-7882840-C-T

Variant summary

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

The NM_030810.5(TXNDC5):​c.*304G>T variant causes a 3 prime UTR 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: TXNDC5 NM_030810.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.677
• Publications: 0 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: 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).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC5	NM_030810.5	MANE Select	c.*304G>T		3_prime_UTR	Exon 10 of 10	NP_110437.2
	TXNDC5	NM_001145549.4		c.*304G>T		3_prime_UTR	Exon 10 of 10	NP_001139021.1	Q8NBS9-2
	BLOC1S5-TXNDC5	NR_037616.1		n.1762G>T		non_coding_transcript_exon	Exon 13 of 13

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC5	ENST00000379757.9	TSL:1 MANE Select	c.*304G>T		3_prime_UTR	Exon 10 of 10	ENSP00000369081.4	Q8NBS9-1
	BLOC1S5-TXNDC5	ENST00000439343.2	TSL:2	n.*1301G>T		non_coding_transcript_exon	Exon 13 of 13	ENSP00000454697.1	H3BN57
	BLOC1S5-TXNDC5	ENST00000439343.2	TSL:2	n.*1301G>T		3_prime_UTR	Exon 13 of 13	ENSP00000454697.1	H3BN57

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 v4.9

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;