rs1058007

Positions:

• chr20-7981481-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021156.4(TMX4):​c.*770G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,924 control chromosomes in the GnomAD database, including 9,242 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 0.25 (9242 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: TMX4 NM_021156.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

Genes affected

TMX4 (HGNC:25237): (thioredoxin related transmembrane protein 4) 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 ER-signal sequence, a catalytically active thioredoxin domain, one transmembrane domain and C-terminal ASP/GLU-rich calcium binding domain. Unlike most members of this gene family, it lacks a C-terminal ER-retention sequence. The encoded protein has been shown to have reductase activity in vitro. [provided by RefSeq, Jan 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMX4	NM_021156.4	c.*770G>A		3_prime_UTR_variant	8/8	ENST00000246024.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMX4	ENST00000246024.7	c.*770G>A		3_prime_UTR_variant	8/8	1	NM_021156.4	P1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38578 AN: 151804 Hom.: 9216 Cov.: 32

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0978

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.0692

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 AFR exome AF: 0.500

GnomAD4 genome AF: 0.254 AC: 38651 AN: 151922 Hom.: 9242 Cov.: 32 AF XY: 0.254 AC XY: 18820 AN XY: 74232

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0978

Gnomad4 NFE AF: 0.0692

Gnomad4 OTH AF: 0.243

Alfa AF: 0.120 Hom.: 2288

Bravo AF: 0.286

Asia WGS AF: 0.337 AC: 1172 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.2
DANN	Benign	0.62

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: rs1058007; hg19: chr20-7962128;