rs1225938

Positions:

• chr6-7886301-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.964-258G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,838 control chromosomes in the GnomAD database, including 10,566 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 0.36 (10566 hom., cov: 31)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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 = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNDC5	NM_030810.5	c.964-258G>A		intron_variant		ENST00000379757.9	NP_110437.2
BLOC1S5-TXNDC5	NR_037616.1	n.1123-258G>A		intron_variant, non_coding_transcript_variant
TXNDC5	NM_001145549.4	c.640-258G>A		intron_variant			NP_001139021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNDC5	ENST00000379757.9	c.964-258G>A		intron_variant		1	NM_030810.5	ENSP00000369081	P1
TXNDC5	ENST00000473453.2	c.640-258G>A		intron_variant		1		ENSP00000420784
TXNDC5	ENST00000460138.5	n.742-258G>A		intron_variant, non_coding_transcript_variant		2
TXNDC5	ENST00000475802.1	n.258-258G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54577 AN: 151720 Hom.: 10545 Cov.: 31

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.360 AC: 54639 AN: 151838 Hom.: 10566 Cov.: 31 AF XY: 0.361 AC XY: 26811 AN XY: 74210

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.649

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.362

Alfa AF: 0.314 Hom.: 987

Bravo AF: 0.383

Asia WGS AF: 0.468 AC: 1627 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	0.70
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1225938; hg19: chr6-7886534;