rs7740689

Positions:

• chr6-7887833-A-G

Variant summary

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

The ENST00000379757.9(TXNDC5):​c.963+872T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0386 in 152,180 control chromosomes in the GnomAD database, including 209 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 0.039 (209 hom., cov: 32)
• Consequence: TXNDC5 ENST00000379757.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.10

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNDC5	NM_030810.5	c.963+872T>C		intron_variant		ENST00000379757.9	NP_110437.2
BLOC1S5-TXNDC5	NR_037616.1	n.1122+872T>C		intron_variant, non_coding_transcript_variant
TXNDC5	NM_001145549.4	c.639+872T>C		intron_variant			NP_001139021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNDC5	ENST00000379757.9	c.963+872T>C		intron_variant		1	NM_030810.5	ENSP00000369081	P1
TXNDC5	ENST00000473453.2	c.639+872T>C		intron_variant		1		ENSP00000420784
TXNDC5	ENST00000460138.5	n.741+872T>C		intron_variant, non_coding_transcript_variant		2
TXNDC5	ENST00000475802.1	n.257+872T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5853 AN: 152062 Hom.: 209 Cov.: 32

Gnomad AFR AF: 0.0957

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0283

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00519

Gnomad FIN AF: 0.00566

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.0359

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

GnomAD4 genome AF: 0.0386 AC: 5867 AN: 152180 Hom.: 209 Cov.: 32 AF XY: 0.0372 AC XY: 2771 AN XY: 74400

Gnomad4 AFR AF: 0.0958

Gnomad4 AMR AF: 0.0282

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00540

Gnomad4 FIN AF: 0.00566

Gnomad4 NFE AF: 0.0177

Gnomad4 OTH AF: 0.0346

Alfa AF: 0.0325 Hom.: 41

Bravo AF: 0.0424

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.056
DANN	Benign	0.49

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: rs7740689; hg19: chr6-7888066;