rs7745225

Variant names:

• chr6-7888018-T-C
• rs7745225
• NM_030810.5:c.963+687A>G

Variant summary

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

The NM_030810.5(TXNDC5):​c.963+687A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0383 in 152,310 control chromosomes in the GnomAD database, including 208 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 0.038 (208 hom., cov: 33)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0924 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.963+687A>G		intron	N/A	NP_110437.2
	TXNDC5	NM_001145549.4		c.639+687A>G		intron	N/A	NP_001139021.1
	BLOC1S5-TXNDC5	NR_037616.1		n.1122+687A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TXNDC5	ENST00000379757.9	TSL:1 MANE Select	c.963+687A>G		intron	N/A	ENSP00000369081.4
	TXNDC5	ENST00000473453.2	TSL:1	c.639+687A>G		intron	N/A	ENSP00000420784.1
	BLOC1S5-TXNDC5	ENST00000439343.2	TSL:2	n.*661+687A>G		intron	N/A	ENSP00000454697.1

Frequencies

GnomAD3 genomes AF: 0.0383 AC: 5824 AN: 152192 Hom.: 208 Cov.: 33

Gnomad AFR AF: 0.0948

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0283

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.00565

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.0359

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

GnomAD4 genome AF: 0.0383 AC: 5836 AN: 152310 Hom.: 208 Cov.: 33 AF XY: 0.0371 AC XY: 2760 AN XY: 74484

African (AFR) AF: 0.0949 AC: 3941 AN: 41548

American (AMR) AF: 0.0282 AC: 432 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 81 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4828

European-Finnish (FIN) AF: 0.00565 AC: 60 AN: 10616

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0178 AC: 1208 AN: 68034

Other (OTH) AF: 0.0346 AC: 73 AN: 2112

Alfa AF: 0.0299 Hom.: 25

Bravo AF: 0.0422

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.091
DANN	Benign	0.43
PhyloP100		-1.8
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: rs7745225; hg19: chr6-7888251;