rs17696707

Variant names:

• chr6-7884009-G-A
• rs17696707
• NM_030810.5:c.1176+350C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-7884009-G-A
• chr6-7884009-G-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.1176+350C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0949 in 152,158 control chromosomes in the GnomAD database, including 728 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 0.095 (728 hom., cov: 32)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TXNDC5	NM_030810.5	c.1176+350C>T		intron_variant	Intron 9 of 9	ENST00000379757.9	NP_110437.2
TXNDC5	NM_001145549.4	c.852+350C>T		intron_variant	Intron 9 of 9		NP_001139021.1
BLOC1S5-TXNDC5	NR_037616.1	n.1335+350C>T		intron_variant	Intron 12 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TXNDC5	ENST00000379757.9	c.1176+350C>T		intron_variant	Intron 9 of 9	1	NM_030810.5	ENSP00000369081.4
BLOC1S5-TXNDC5	ENST00000439343.2	n.*874+350C>T		intron_variant	Intron 12 of 12	2		ENSP00000454697.1

Frequencies

GnomAD3 genomes AF: 0.0948 AC: 14416 AN: 152040 Hom.: 723 Cov.: 32

Gnomad AFR AF: 0.0845

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0780

Gnomad ASJ AF: 0.0686

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0938

Gnomad OTH AF: 0.0903

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

GnomAD4 genome AF: 0.0949 AC: 14438 AN: 152158 Hom.: 728 Cov.: 32 AF XY: 0.0981 AC XY: 7297 AN XY: 74390

African (AFR) AF: 0.0846 AC: 3510 AN: 41502

American (AMR) AF: 0.0779 AC: 1192 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0686 AC: 238 AN: 3470

East Asian (EAS) AF: 0.109 AC: 561 AN: 5168

South Asian (SAS) AF: 0.105 AC: 504 AN: 4822

European-Finnish (FIN) AF: 0.166 AC: 1761 AN: 10582

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0938 AC: 6376 AN: 68000

Other (OTH) AF: 0.0940 AC: 199 AN: 2116

Alfa AF: 0.0810 Hom.: 272

Bravo AF: 0.0895

Asia WGS AF: 0.133 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.022
DANN	Benign	0.66
PhyloP100		-2.4
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: rs17696707; hg19: chr6-7884242;