Variant 18-68687488-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000299608.7(TMX3):c.736+179C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0384 in 984,896 control chromosomes in the GnomAD database, including 5,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.13 ( 4027 hom., cov: 33)

Exomes 𝑓: 0.021 ( 1936 hom. )

Consequence

TMX3
ENST00000299608.7 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.423

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:

TMX3 (HGNC:):

TMX3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 18-68687488-G-A is Benign according to our data. Variant chr18-68687488-G-A is described in ClinVar as [Benign]. Clinvar id is 1258686.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 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.736+179C>T		intron_variant		ENST00000299608.7	NP_061895.3	Q96JJ7-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
TMX3	ENST00000299608.7 linkuse as main transcript	c.736+179C>T	intron_variant	1	NM_019022.5	ENSP00000299608.2	Q96JJ7-1
TMX3	ENST00000564631.5 linkuse as main transcript	n.*420+179C>T	intron_variant	1		ENSP00000456587.1	H3BVI1
TMX3	ENST00000578765.1 linkuse as main transcript	n.311+179C>T	intron_variant	4

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20171

AN:

151970

Hom.:

4019

Cov.:

show subpopulations

Gnomad AFR

AF:

0.431

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0685

Gnomad ASJ

AF:

0.00982

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00601

Gnomad FIN

AF:

0.00340

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.104

GnomAD4 exome

AF:

0.0212

AC:

17646

AN:

832808

Hom.:

1936

Cov.:

AF XY:

0.0206

AC XY:

7913

AN XY:

384584

show subpopulations

Gnomad4 AFR exome

AF:

0.473

Gnomad4 AMR exome

AF:

0.0418

Gnomad4 ASJ exome

AF:

0.0122

Gnomad4 EAS exome

AF:

0.000551

Gnomad4 SAS exome

AF:

0.00352

Gnomad4 FIN exome

AF:

0.00725

Gnomad4 NFE exome

AF:

0.0118

Gnomad4 OTH exome

AF:

0.0363

GnomAD4 genome

AF:

0.133

AC:

20214

AN:

152088

Hom.:

4027

Cov.:

AF XY:

0.128

AC XY:

9487

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.431

Gnomad4 AMR

AF:

0.0683

Gnomad4 ASJ

AF:

0.00982

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00602

Gnomad4 FIN

AF:

0.00340

Gnomad4 NFE

AF:

0.0133

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.0835

Hom.:

287

Bravo

AF:

0.152

Asia WGS

AF:

0.0290

AC:

103

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

3.6

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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