Variant 18-68687906-GCATA-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_019022.5(TMX3):c.638-145_638-142del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 512,326 control chromosomes in the GnomAD database, including 528 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.042 ( 424 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 104 hom. )

Consequence

TMX3
NM_019022.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.433

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 18-68687906-GCATA-G is Benign according to our data. Variant chr18-68687906-GCATA-G is described in ClinVar as [Benign]. Clinvar id is 1178895.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 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.638-145_638-142del		intron_variant		ENST00000299608.7	NP_061895.3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMX3	ENST00000299608.7 linkuse as main transcript	c.638-145_638-142del	intron_variant		1	NM_019022.5	ENSP00000299608	P1	Q96JJ7-1
TMX3	ENST00000564631.5 linkuse as main transcript	c.322-145_322-142del	intron_variant, NMD_transcript_variant		1		ENSP00000456587
TMX3	ENST00000578765.1 linkuse as main transcript	n.68_71del	non_coding_transcript_exon_variant	1/4	4

Frequencies

GnomAD3 genomes

AF:

0.0415

AC:

6301

AN:

151874

Hom.:

420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0172

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.0331

GnomAD4 exome

AF:

0.00493

AC:

1775

AN:

360336

Hom.:

104

AF XY:

0.00419

AC XY:

782

AN XY:

186676

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.0129

Gnomad4 ASJ exome

AF:

0.00503

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000399

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000407

Gnomad4 OTH exome

AF:

0.0120

GnomAD4 genome

AF:

0.0416

AC:

6318

AN:

151990

Hom.:

424

Cov.:

AF XY:

0.0402

AC XY:

2985

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.143

Gnomad4 AMR

AF:

0.0172

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.0328

Alfa

AF:

0.0316

Hom.:

Bravo

AF:

0.0472

Asia WGS

AF:

0.00665

AC:

AN:

3474

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 28, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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