chr6-7899795-T-C

Variant names:

• chr6-7899795-T-C
• rs1225954
• NM_030810.5:c.414-114A>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.414-114A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 641,936 control chromosomes in the GnomAD database, including 38,612 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 0.37 (11773 hom., cov: 33)
  • Exomes 𝑓: 0.31 (26839 hom.)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.399
• Publications: 5 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNDC5	NM_030810.5	c.414-114A>G		intron_variant	Intron 2 of 9	ENST00000379757.9	NP_110437.2
TXNDC5	NM_001145549.4	c.90-114A>G		intron_variant	Intron 2 of 9		NP_001139021.1
BLOC1S5-TXNDC5	NR_037616.1	n.573-114A>G		intron_variant	Intron 5 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNDC5	ENST00000379757.9	c.414-114A>G		intron_variant	Intron 2 of 9	1	NM_030810.5	ENSP00000369081.4
TXNDC5	ENST00000473453.2	c.90-114A>G		intron_variant	Intron 2 of 9	1		ENSP00000420784.1
BLOC1S5-TXNDC5	ENST00000439343.2	n.*112-114A>G		intron_variant	Intron 5 of 12	2		ENSP00000454697.1
TXNDC5	ENST00000469459.1	n.448A>G		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56124 AN: 152098 Hom.: 11747 Cov.: 33

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.306 AC: 150004 AN: 489720 Hom.: 26839 Cov.: 7 AF XY: 0.302 AC XY: 77701 AN XY: 257242

African (AFR) AF: 0.524 AC: 6710 AN: 12810

American (AMR) AF: 0.516 AC: 9807 AN: 18996

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 2975 AN: 14140

East Asian (EAS) AF: 0.694 AC: 20179 AN: 29080

South Asian (SAS) AF: 0.276 AC: 11329 AN: 41066

European-Finnish (FIN) AF: 0.258 AC: 8431 AN: 32698

Middle Eastern (MID) AF: 0.269 AC: 978 AN: 3640

European-Non Finnish (NFE) AF: 0.261 AC: 80953 AN: 310328

Other (OTH) AF: 0.321 AC: 8642 AN: 26962

GnomAD4 genome AF: 0.369 AC: 56205 AN: 152216 Hom.: 11773 Cov.: 33 AF XY: 0.372 AC XY: 27675 AN XY: 74414

African (AFR) AF: 0.523 AC: 21705 AN: 41510

American (AMR) AF: 0.465 AC: 7116 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 733 AN: 3466

East Asian (EAS) AF: 0.649 AC: 3371 AN: 5192

South Asian (SAS) AF: 0.295 AC: 1424 AN: 4826

European-Finnish (FIN) AF: 0.258 AC: 2729 AN: 10598

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17866 AN: 68014

Other (OTH) AF: 0.358 AC: 756 AN: 2114

Alfa AF: 0.318 Hom.: 1121

Bravo AF: 0.396

Asia WGS AF: 0.473 AC: 1644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.76
PhyloP100		-0.40
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: rs1225954; hg19: chr6-7900028;