NM_030810.5:c.617-174G>C

Variant names:

• chr6-7891910-C-G
• rs1225950
• NM_030810.5:c.617-174G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030810.5(TXNDC5):​c.617-174G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,136 control chromosomes in the GnomAD database, including 23,394 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 0.52 (23394 hom., cov: 33)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410
• Publications: 3 publications found

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 -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 = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNDC5	NM_030810.5	c.617-174G>C		intron_variant	Intron 4 of 9	ENST00000379757.9	NP_110437.2
TXNDC5	NM_001145549.4	c.293-174G>C		intron_variant	Intron 4 of 9		NP_001139021.1
BLOC1S5-TXNDC5	NR_037616.1	n.776-174G>C		intron_variant	Intron 7 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNDC5	ENST00000379757.9	c.617-174G>C		intron_variant	Intron 4 of 9	1	NM_030810.5	ENSP00000369081.4
TXNDC5	ENST00000473453.2	c.293-174G>C		intron_variant	Intron 4 of 9	1		ENSP00000420784.1
BLOC1S5-TXNDC5	ENST00000439343.2	n.*315-174G>C		intron_variant	Intron 7 of 12	2		ENSP00000454697.1

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79338 AN: 152018 Hom.: 23340 Cov.: 33

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.765

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.522 AC: 79455 AN: 152136 Hom.: 23394 Cov.: 33 AF XY: 0.527 AC XY: 39159 AN XY: 74354

African (AFR) AF: 0.780 AC: 32389 AN: 41526

American (AMR) AF: 0.576 AC: 8805 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1042 AN: 3468

East Asian (EAS) AF: 0.765 AC: 3955 AN: 5170

South Asian (SAS) AF: 0.405 AC: 1952 AN: 4820

European-Finnish (FIN) AF: 0.429 AC: 4531 AN: 10572

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25131 AN: 67984

Other (OTH) AF: 0.493 AC: 1039 AN: 2108

Alfa AF: 0.449 Hom.: 2147

Bravo AF: 0.549

Asia WGS AF: 0.621 AC: 2158 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	1.0
DANN	Benign	0.43
PhyloP100		-0.41
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

Other links and lift over

dbSNP: rs1225950; hg19: chr6-7892143;