rs6133519

Variant names:

• chr20-7980218-G-A
• rs6133519
• NM_021156.4:c.*2033C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021156.4(TMX4):​c.*2033C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 152,004 control chromosomes in the GnomAD database, including 2,309 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 0.14 (2309 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMX4 NM_021156.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021156.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMX4	NM_021156.4	MANE Select	c.*2033C>T		3_prime_UTR	Exon 8 of 8	NP_066979.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMX4	ENST00000246024.7	TSL:1 MANE Select	c.*2033C>T		3_prime_UTR	Exon 8 of 8	ENSP00000246024.2

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21270 AN: 151886 Hom.: 2309 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.0556

Gnomad FIN AF: 0.0977

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.153

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

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) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.140 AC: 21283 AN: 152004 Hom.: 2309 Cov.: 32 AF XY: 0.142 AC XY: 10562 AN XY: 74300

African (AFR) AF: 0.243 AC: 10057 AN: 41394

American (AMR) AF: 0.120 AC: 1837 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 418 AN: 3468

East Asian (EAS) AF: 0.528 AC: 2730 AN: 5172

South Asian (SAS) AF: 0.0555 AC: 267 AN: 4812

European-Finnish (FIN) AF: 0.0977 AC: 1033 AN: 10572

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0672 AC: 4571 AN: 67990

Other (OTH) AF: 0.153 AC: 323 AN: 2108

Alfa AF: 0.111 Hom.: 227

Bravo AF: 0.153

Asia WGS AF: 0.267 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.45
PhyloP100		-0.032
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: rs6133519; hg19: chr20-7960865;