rs368074

Variant names:

• chr6-7899336-C-G
• rs368074
• NM_030810.5:c.519+240G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-7899336-C-G
• chr6-7899336-C-T

Variant summary

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

The NM_030810.5(TXNDC5):​c.519+240G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,058 control chromosomes in the GnomAD database, including 7,963 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 0.31 (7963 hom., cov: 32)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC5	NM_030810.5	MANE Select	c.519+240G>C		intron	N/A	NP_110437.2
	TXNDC5	NM_001145549.4		c.195+240G>C		intron	N/A	NP_001139021.1	Q8NBS9-2
	BLOC1S5-TXNDC5	NR_037616.1		n.678+240G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC5	ENST00000379757.9	TSL:1 MANE Select	c.519+240G>C		intron	N/A	ENSP00000369081.4	Q8NBS9-1
	TXNDC5	ENST00000473453.2	TSL:1	c.195+240G>C		intron	N/A	ENSP00000420784.1	Q8NBS9-2
	BLOC1S5-TXNDC5	ENST00000439343.2	TSL:2	n.*217+240G>C		intron	N/A	ENSP00000454697.1	H3BN57

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46889 AN: 151940 Hom.: 7951 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.309 AC: 46935 AN: 152058 Hom.: 7963 Cov.: 32 AF XY: 0.313 AC XY: 23248 AN XY: 74330

African (AFR) AF: 0.331 AC: 13712 AN: 41472

American (AMR) AF: 0.434 AC: 6632 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 716 AN: 3472

East Asian (EAS) AF: 0.649 AC: 3355 AN: 5172

South Asian (SAS) AF: 0.294 AC: 1417 AN: 4826

European-Finnish (FIN) AF: 0.253 AC: 2674 AN: 10560

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17268 AN: 67966

Other (OTH) AF: 0.318 AC: 670 AN: 2110

Alfa AF: 0.271 Hom.: 747

Bravo AF: 0.328

Asia WGS AF: 0.456 AC: 1582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.47
DANN	Benign	0.39
PhyloP100		-0.42
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: rs368074; hg19: chr6-7899569;