rs17696707

chr6-7884009-G-Achr6-7884009-G-C

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
TXNDC5	NM_030810.5	c.1176+350C>T		intron_variant		ENST00000379757.9
BLOC1S5-TXNDC5	NR_037616.1	n.1335+350C>T		intron_variant, non_coding_transcript_variant
TXNDC5	NM_001145549.4	c.852+350C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TXNDC5	ENST00000379757.9	c.1176+350C>T		intron_variant		1	NM_030810.5	P1
TXNDC5	ENST00000473453.2	c.852+350C>T		intron_variant		1
TXNDC5	ENST00000460138.5	n.954+350C>T		intron_variant, non_coding_transcript_variant		2
TXNDC5	ENST00000475802.1	n.470+350C>T		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.0846

Gnomad4 AMR AF: 0.0779

Gnomad4 ASJ AF: 0.0686

Gnomad4 EAS AF: 0.109

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.0938

Gnomad4 OTH AF: 0.0940

Alfa AF: 0.0797 Hom.: 231

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs17696707; hg19: chr6-7884242;