Variant 18-68691247-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019022.5(TMX3):c.637+48G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,326,834 control chromosomes in the GnomAD database, including 1,494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 848 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 646 hom. )

Consequence

TMX3
NM_019022.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.160

Variant links:

Genes affected

TMX3 (HGNC:24718): (thioredoxin related transmembrane protein 3) 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 canonical protein encoded by this gene has an N-terminal ER-signal sequence, a catalytically active thioredoxin domain, one transmembrane domain and a C-terminal ER-retention sequence. This gene is expressed in many tissues but has its highest expression in heart and skeletal muscle. It is expressed in the retinal neuroepithelium and lens epithelium in the developing murine eye and haploinsufficiency of this gene in humans and zebrafish is associated with microphthalmia. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2017]

TMX3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 18-68691247-C-T is Benign according to our data. Variant chr18-68691247-C-T is described in ClinVar as [Benign]. Clinvar id is 1280904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMX3	NM_019022.5 linkuse as main transcript	c.637+48G>A		intron_variant		ENST00000299608.7	NP_061895.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMX3	ENST00000299608.7 linkuse as main transcript	c.637+48G>A		intron_variant		1	NM_019022.5	ENSP00000299608	P1	Q96JJ7-1

Frequencies

GnomAD3 genomes

AF:

0.0600

AC:

9108

AN:

151860

Hom.:

841

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0367

Gnomad ASJ

AF:

0.00721

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.0287

Gnomad NFE

AF:

0.00178

Gnomad OTH

AF:

0.0537

GnomAD3 exomes

AF:

0.0168

AC:

2877

AN:

171102

Hom.:

231

AF XY:

0.0132

AC XY:

1213

AN XY:

91746

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.0174

Gnomad ASJ exome

AF:

0.00705

Gnomad EAS exome

AF:

0.0000739

Gnomad SAS exome

AF:

0.000679

Gnomad FIN exome

AF:

0.000109

Gnomad NFE exome

AF:

0.00189

Gnomad OTH exome

AF:

0.0116

GnomAD4 exome

AF:

0.00765

AC:

8982

AN:

1174854

Hom.:

646

Cov.:

AF XY:

0.00696

AC XY:

4088

AN XY:

587598

show subpopulations

Gnomad4 AFR exome

AF:

0.210

Gnomad4 AMR exome

AF:

0.0195

Gnomad4 ASJ exome

AF:

0.00752

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000690

Gnomad4 FIN exome

AF:

0.0000815

Gnomad4 NFE exome

AF:

0.00163

Gnomad4 OTH exome

AF:

0.0183

GnomAD4 genome

AF:

0.0601

AC:

9129

AN:

151980

Hom.:

848

Cov.:

AF XY:

0.0588

AC XY:

4366

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.200

Gnomad4 AMR

AF:

0.0366

Gnomad4 ASJ

AF:

0.00721

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.000284

Gnomad4 NFE

AF:

0.00178

Gnomad4 OTH

AF:

0.0531

Alfa

AF:

0.0281

Hom.:

Bravo

AF:

0.0696

Asia WGS

AF:

0.0100

AC:

AN:

3462

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

4.6

DANN

Benign

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over