rs9502656

Variant names:

• chr6-7883153-G-A
• rs9502656
• NM_030810.5:c.1290C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-7883153-G-A
• chr6-7883153-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_030810.5(TXNDC5):​c.1290C>T​(p.Asp430Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0279 in 1,614,084 control chromosomes in the GnomAD database, including 2,118 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 0.074 (1003 hom., cov: 32)
  • Exomes 𝑓: 0.023 (1115 hom.)
• Consequence: TXNDC5 NM_030810.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.768

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:42001): (BLOC1S5-TXNDC5 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring MUTED (muted homolog) and TXNDC5 (thioredoxin domain containing 5) genes on chromosome 6. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-0.768 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNDC5	NM_030810.5	c.1290C>T	p.Asp430Asp	synonymous_variant	Exon 10 of 10	ENST00000379757.9	NP_110437.2
TXNDC5	NM_001145549.4	c.966C>T	p.Asp322Asp	synonymous_variant	Exon 10 of 10		NP_001139021.1
BLOC1S5-TXNDC5	NR_037616.1	n.1449C>T		non_coding_transcript_exon_variant	Exon 13 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNDC5	ENST00000379757.9	c.1290C>T	p.Asp430Asp	synonymous_variant	Exon 10 of 10	1	NM_030810.5	ENSP00000369081.4
BLOC1S5-TXNDC5	ENST00000439343.2	n.*988C>T		non_coding_transcript_exon_variant	Exon 13 of 13	2		ENSP00000454697.1
BLOC1S5-TXNDC5	ENST00000439343.2	n.*988C>T		3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000454697.1

Frequencies

GnomAD3 genomes AF: 0.0736 AC: 11193 AN: 152106 Hom.: 1003 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.00593

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0188

Gnomad OTH AF: 0.0618

GnomAD2 exomes AF: 0.0295 AC: 7429 AN: 251442 AF XY: 0.0252

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.0258

Gnomad ASJ exome AF: 0.0266

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00688

Gnomad NFE exome AF: 0.0196

Gnomad OTH exome AF: 0.0256

GnomAD4 exome AF: 0.0232 AC: 33843 AN: 1461860 Hom.: 1115 Cov.: 30 AF XY: 0.0222 AC XY: 16137 AN XY: 727234

Gnomad4 AFR exome AF: 0.220 AC: 7361 AN: 33476

Gnomad4 AMR exome AF: 0.0269 AC: 1203 AN: 44724

Gnomad4 ASJ exome AF: 0.0250 AC: 654 AN: 26136

Gnomad4 EAS exome AF: 0.0000252 AC: 1 AN: 39698

Gnomad4 SAS exome AF: 0.00777 AC: 670 AN: 86258

Gnomad4 FIN exome AF: 0.00753 AC: 402 AN: 53408

Gnomad4 NFE exome AF: 0.0193 AC: 21517 AN: 1112002

Gnomad4 Remaining exome AF: 0.0298 AC: 1801 AN: 60392

GnomAD4 genome AF: 0.0736 AC: 11208 AN: 152224 Hom.: 1003 Cov.: 32 AF XY: 0.0723 AC XY: 5381 AN XY: 74436

Gnomad4 AFR AF: 0.214 AC: 0.214028 AN: 0.214028

Gnomad4 AMR AF: 0.0466 AC: 0.0466196 AN: 0.0466196

Gnomad4 ASJ AF: 0.0280 AC: 0.0279539 AN: 0.0279539

Gnomad4 EAS AF: 0.000193 AC: 0.000192901 AN: 0.000192901

Gnomad4 SAS AF: 0.00539 AC: 0.00538748 AN: 0.00538748

Gnomad4 FIN AF: 0.00593 AC: 0.00593444 AN: 0.00593444

Gnomad4 NFE AF: 0.0187 AC: 0.0187461 AN: 0.0187461

Gnomad4 OTH AF: 0.0602 AC: 0.0601896 AN: 0.0601896

Alfa AF: 0.0471 Hom.: 287

Bravo AF: 0.0828

Asia WGS AF: 0.0150 AC: 54 AN: 3478

EpiCase AF: 0.0218

EpiControl AF: 0.0220

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.29
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs9502656; hg19: chr6-7883386;