rs408014

Positions:

• chr6-7899161-G-A
• chr6-7899161-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.519+415C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,018 control chromosomes in the GnomAD database, including 8,118 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 (8118 hom., cov: 32)
• Consequence: TXNDC5 NM_030810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TXNDC5	NM_030810.5	c.519+415C>T		intron_variant		ENST00000379757.9	NP_110437.2
BLOC1S5-TXNDC5	NR_037616.1	n.678+415C>T		intron_variant, non_coding_transcript_variant
TXNDC5	NM_001145549.4	c.195+415C>T		intron_variant			NP_001139021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TXNDC5	ENST00000379757.9	c.519+415C>T		intron_variant		1	NM_030810.5	ENSP00000369081	P1
TXNDC5	ENST00000473453.2	c.195+415C>T		intron_variant		1		ENSP00000420784
TXNDC5	ENST00000469459.1	n.667+415C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47499 AN: 151900 Hom.: 8103 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.313 AC: 47553 AN: 152018 Hom.: 8118 Cov.: 32 AF XY: 0.316 AC XY: 23487 AN XY: 74286

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.319

Alfa AF: 0.278 Hom.: 772

Bravo AF: 0.332

Asia WGS AF: 0.459 AC: 1593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.093
DANN	Benign	0.58

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: rs408014; hg19: chr6-7899394;