rs7764128

Positions:

• chr6-7881972-G-A

Variant summary

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

The NM_030810.5(TXNDC5):​c.*1172C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,584 control chromosomes in the GnomAD database, including 4,809 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 0.21 (4805 hom., cov: 32)
  • Exomes 𝑓: 0.15 (4 hom.)
• Consequence: TXNDC5 NM_030810.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TXNDC5	NM_030810.5	c.*1172C>T		3_prime_UTR_variant	10/10	ENST00000379757.9
BLOC1S5-TXNDC5	NR_037616.1	n.2630C>T		non_coding_transcript_exon_variant	13/13
TXNDC5	NM_001145549.4	c.*1172C>T		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNDC5	ENST00000379757.9	c.*1172C>T		3_prime_UTR_variant	10/10	1	NM_030810.5	P1
TXNDC5	ENST00000460138.5	n.2249C>T		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31576 AN: 152022 Hom.: 4785 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.149 AC: 66 AN: 444 Hom.: 4 Cov.: 0 AF XY: 0.159 AC XY: 43 AN XY: 270

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.208 AC: 31645 AN: 152140 Hom.: 4805 Cov.: 32 AF XY: 0.208 AC XY: 15463 AN XY: 74392

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0965

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.179

Alfa AF: 0.162 Hom.: 669

Bravo AF: 0.218

Asia WGS AF: 0.155 AC: 540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7764128; hg19: chr6-7882205;