rs420970

Positions:

• chr6-7899418-G-A

Variant summary

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

The NM_030810.5(TXNDC5):​c.519+158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,684 control chromosomes in the GnomAD database, including 19,967 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 0.49 (19967 hom., cov: 31)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNDC5	NM_030810.5	c.519+158C>T		intron_variant		ENST00000379757.9	NP_110437.2
TXNDC5	NM_001145549.4	c.195+158C>T		intron_variant			NP_001139021.1
BLOC1S5-TXNDC5	NR_037616.1	n.678+158C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNDC5	ENST00000379757.9	c.519+158C>T		intron_variant		1	NM_030810.5	ENSP00000369081.4
TXNDC5	ENST00000473453.2	c.195+158C>T		intron_variant		1		ENSP00000420784.1
BLOC1S5-TXNDC5	ENST00000439343.2	n.*217+158C>T		intron_variant		2		ENSP00000454697.1
TXNDC5	ENST00000469459.1	n.667+158C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74004 AN: 151566 Hom.: 19922 Cov.: 31

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.355

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.489 AC: 74111 AN: 151684 Hom.: 19967 Cov.: 31 AF XY: 0.494 AC XY: 36611 AN XY: 74108

Gnomad4 AFR AF: 0.694

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.763

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.463

Alfa AF: 0.428 Hom.: 1891

Bravo AF: 0.514

Asia WGS AF: 0.613 AC: 2129 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.28

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: rs420970; hg19: chr6-7899651;