rs1058007

Variant names:

• chr20-7981481-C-T
• rs1058007
• NM_021156.4:c.*770G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TMX4	NM_021156.4	c.*770G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000246024.7	NP_066979.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMX4	ENST00000246024.7	c.*770G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_021156.4	ENSP00000246024.2

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

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.603 AC: 24993 AN: 41418

American (AMR) AF: 0.223 AC: 3408 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 413 AN: 3466

East Asian (EAS) AF: 0.591 AC: 3042 AN: 5146

South Asian (SAS) AF: 0.102 AC: 491 AN: 4816

European-Finnish (FIN) AF: 0.0978 AC: 1029 AN: 10522

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.0692 AC: 4700 AN: 67954

Other (OTH) AF: 0.243 AC: 512 AN: 2110

Alfa AF: 0.150 Hom.: 10554

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
PhyloP100		1.4
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: rs1058007; hg19: chr20-7962128;