rs1225955

chr6-7900476-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.414-795T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,056 control chromosomes in the GnomAD database, including 14,032 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 0.40 (14032 hom., cov: 33)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNDC5	NM_030810.5	c.414-795T>C		intron_variant		ENST00000379757.9
BLOC1S5-TXNDC5	NR_037616.1	n.573-795T>C		intron_variant, non_coding_transcript_variant
TXNDC5	NM_001145549.4	c.90-795T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNDC5	ENST00000379757.9	c.414-795T>C		intron_variant		1	NM_030810.5	P1
TXNDC5	ENST00000473453.2	c.90-795T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60867 AN: 151938 Hom.: 14002 Cov.: 33

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.387

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

GnomAD4 genome AF: 0.401 AC: 60954 AN: 152056 Hom.: 14032 Cov.: 33 AF XY: 0.403 AC XY: 29934 AN XY: 74354

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.490

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.388

Alfa AF: 0.334 Hom.: 1207

Bravo AF: 0.430

Asia WGS AF: 0.480 AC: 1667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.9
Dann	Benign	0.70

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: rs1225955; hg19: chr6-7900709; COSMIC: COSV65730916; COSMIC: COSV65730916;