chr6-7882840-C-T

Position:

• chr6-7882840-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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

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]

TXNDC5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TXNDC5	NM_030810.5	c.*304G>A		3_prime_UTR_variant	10/10	ENST00000379757.9	NP_110437.2
TXNDC5	NM_001145549.4	c.*304G>A		3_prime_UTR_variant	10/10		NP_001139021.1
BLOC1S5-TXNDC5	NR_037616.1	n.1762G>A		non_coding_transcript_exon_variant	13/13

Ensembl

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

Gnomad4 AFR exome AF: 0.0719

Gnomad4 AMR exome AF: 0.0972

Gnomad4 ASJ exome AF: 0.0618

Gnomad4 EAS exome AF: 0.0856

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.143

Gnomad4 NFE exome AF: 0.0893

Gnomad4 OTH exome AF: 0.0899

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

Gnomad4 AFR AF: 0.0737

Gnomad4 AMR AF: 0.0770

Gnomad4 ASJ AF: 0.0686

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.0939

Gnomad4 OTH AF: 0.0907

Alfa AF: 0.0930 Hom.: 332

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs8643; hg19: chr6-7883073;