rs9505301

Positions:

• chr6-7886898-A-G

Variant summary

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

The NM_030810.5(TXNDC5):​c.964-855T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,096 control chromosomes in the GnomAD database, including 3,056 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 0.18 (3056 hom., cov: 32)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNDC5	NM_030810.5	c.964-855T>C		intron_variant		ENST00000379757.9	NP_110437.2
TXNDC5	NM_001145549.4	c.640-855T>C		intron_variant			NP_001139021.1
BLOC1S5-TXNDC5	NR_037616.1	n.1123-855T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNDC5	ENST00000379757.9	c.964-855T>C		intron_variant		1	NM_030810.5	ENSP00000369081.4
BLOC1S5-TXNDC5	ENST00000439343.2	n.*662-855T>C		intron_variant		2		ENSP00000454697.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26669 AN: 151978 Hom.: 3046 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.176 AC: 26729 AN: 152096 Hom.: 3056 Cov.: 32 AF XY: 0.179 AC XY: 13300 AN XY: 74372

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.0925

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.145

Alfa AF: 0.141 Hom.: 861

Bravo AF: 0.180

Asia WGS AF: 0.170 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	15
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9505301; hg19: chr6-7887131;