NM_030810.5:c.733-307A>C

Variant names:

• chr6-7889888-T-G
• rs1225947
• NM_030810.5:c.733-307A>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.733-307A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 151,996 control chromosomes in the GnomAD database, including 13,305 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 0.40 (13305 hom., cov: 32)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030810.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC5	NM_030810.5	MANE Select	c.733-307A>C		intron	N/A	NP_110437.2
	TXNDC5	NM_001145549.4		c.409-307A>C		intron	N/A	NP_001139021.1
	BLOC1S5-TXNDC5	NR_037616.1		n.892-307A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC5	ENST00000379757.9	TSL:1 MANE Select	c.733-307A>C		intron	N/A	ENSP00000369081.4
	TXNDC5	ENST00000473453.2	TSL:1	c.409-307A>C		intron	N/A	ENSP00000420784.1
	BLOC1S5-TXNDC5	ENST00000439343.2	TSL:2	n.*431-307A>C		intron	N/A	ENSP00000454697.1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60003 AN: 151878 Hom.: 13270 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.395 AC: 60091 AN: 151996 Hom.: 13305 Cov.: 32 AF XY: 0.397 AC XY: 29458 AN XY: 74294

African (AFR) AF: 0.561 AC: 23257 AN: 41438

American (AMR) AF: 0.485 AC: 7408 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 802 AN: 3472

East Asian (EAS) AF: 0.651 AC: 3362 AN: 5162

South Asian (SAS) AF: 0.313 AC: 1502 AN: 4802

European-Finnish (FIN) AF: 0.265 AC: 2797 AN: 10572

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19627 AN: 67958

Other (OTH) AF: 0.390 AC: 825 AN: 2114

Alfa AF: 0.367 Hom.: 1701

Bravo AF: 0.422

Asia WGS AF: 0.486 AC: 1690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.42
DANN	Benign	0.31
PhyloP100		-1.3
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: rs1225947; hg19: chr6-7890121;