Variant 18-68691166-G-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+129C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 506,102 control chromosomes in the GnomAD database, including 8,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 5011 hom., cov: 32)

Exomes 𝑓: 0.12 ( 3497 hom. )

Consequence

TMX3
NM_019022.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.465

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 18-68691166-G-T is Benign according to our data. Variant chr18-68691166-G-T is described in ClinVar as [Benign]. Clinvar id is 1274094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 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+129C>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+129C>A		intron_variant		1	NM_019022.5	ENSP00000299608	P1	Q96JJ7-1

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32086

AN:

151688

Hom.:

4996

Cov.:

show subpopulations

Gnomad AFR

AF:

0.440

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.190

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.162

Gnomad SAS

AF:

0.0625

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.211

GnomAD4 exome

AF:

0.123

AC:

43441

AN:

354294

Hom.:

3497

Cov.:

AF XY:

0.122

AC XY:

21734

AN XY:

178734

show subpopulations

Gnomad4 AFR exome

AF:

0.443

Gnomad4 AMR exome

AF:

0.197

Gnomad4 ASJ exome

AF:

0.194

Gnomad4 EAS exome

AF:

0.184

Gnomad4 SAS exome

AF:

0.0547

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.0984

Gnomad4 OTH exome

AF:

0.148

GnomAD4 genome

AF:

0.212

AC:

32146

AN:

151808

Hom.:

5011

Cov.:

AF XY:

0.211

AC XY:

15630

AN XY:

74176

show subpopulations

Gnomad4 AFR

AF:

0.440

Gnomad4 AMR

AF:

0.191

Gnomad4 ASJ

AF:

0.193

Gnomad4 EAS

AF:

0.162

Gnomad4 SAS

AF:

0.0620

Gnomad4 FIN

AF:

0.144

Gnomad4 NFE

AF:

0.103

Gnomad4 OTH

AF:

0.210

Alfa

AF:

0.137

Hom.:

1963

Bravo

AF:

0.232

Asia WGS

AF:

0.156

AC:

546

AN:

3474

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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.2

DANN

Benign

0.67

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