rs1225954

chr6-7899795-T-C

Variant summary

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

The NM_030810.5(TXNDC5):c.414-114A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 641,936 control chromosomes in the GnomAD database, including 38,612 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 0.37 (11773 hom., cov: 33)
  • Exomes 𝑓: 0.31 (26839 hom.)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNDC5	NM_030810.5	c.414-114A>G		intron_variant		ENST00000379757.9
BLOC1S5-TXNDC5	NR_037616.1	n.573-114A>G		intron_variant, non_coding_transcript_variant
TXNDC5	NM_001145549.4	c.90-114A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNDC5	ENST00000379757.9	c.414-114A>G		intron_variant		1	NM_030810.5	P1
TXNDC5	ENST00000473453.2	c.90-114A>G		intron_variant		1
TXNDC5	ENST00000469459.1	n.448A>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56124 AN: 152098 Hom.: 11747 Cov.: 33

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.306 AC: 150004 AN: 489720 Hom.: 26839 Cov.: 7 AF XY: 0.302 AC XY: 77701 AN XY: 257242

Gnomad4 AFR exome AF: 0.524

Gnomad4 AMR exome AF: 0.516

Gnomad4 ASJ exome AF: 0.210

Gnomad4 EAS exome AF: 0.694

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.321

GnomAD4 genome AF: 0.369 AC: 56205 AN: 152216 Hom.: 11773 Cov.: 33 AF XY: 0.372 AC XY: 27675 AN XY: 74414

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.649

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.358

Alfa AF: 0.310 Hom.: 1017

Bravo AF: 0.396

Asia WGS AF: 0.473 AC: 1644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.7
Dann	Benign	0.76

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: rs1225954; hg19: chr6-7900028;