Variant 18-68687521-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_019022.5(TMX3):c.736+146T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 1,417,060 control chromosomes in the GnomAD database, including 10,202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 5811 hom., cov: 33)

Exomes 𝑓: 0.026 ( 4391 hom. )

Consequence

TMX3
NM_019022.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.30

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 18-68687521-A-G is Benign according to our data. Variant chr18-68687521-A-G is described in ClinVar as [Benign]. Clinvar id is 1276569.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 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+146T>C		intron_variant		ENST00000299608.7	NP_061895.3

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
TMX3	ENST00000299608.7 linkuse as main transcript	c.736+146T>C	intron_variant	1	NM_019022.5	ENSP00000299608	P1	Q96JJ7-1
TMX3	ENST00000564631.5 linkuse as main transcript	c.*420+146T>C	intron_variant, NMD_transcript_variant	1		ENSP00000456587
TMX3	ENST00000578765.1 linkuse as main transcript	n.311+146T>C	intron_variant, non_coding_transcript_variant	4

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24235

AN:

152064

Hom.:

5785

Cov.:

show subpopulations

Gnomad AFR

AF:

0.518

Gnomad AMI

AF:

0.0625

Gnomad AMR

AF:

0.0813

Gnomad ASJ

AF:

0.0107

Gnomad EAS

AF:

0.0156

Gnomad SAS

AF:

0.0103

Gnomad FIN

AF:

0.00330

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0149

Gnomad OTH

AF:

0.123

GnomAD4 exome

AF:

0.0259

AC:

32716

AN:

1264878

Hom.:

4391

Cov.:

AF XY:

0.0244

AC XY:

15046

AN XY:

616036

show subpopulations

Gnomad4 AFR exome

AF:

0.544

Gnomad4 AMR exome

AF:

0.0590

Gnomad4 ASJ exome

AF:

0.0125

Gnomad4 EAS exome

AF:

0.0180

Gnomad4 SAS exome

AF:

0.00709

Gnomad4 FIN exome

AF:

0.00432

Gnomad4 NFE exome

AF:

0.0129

Gnomad4 OTH exome

AF:

0.0499

GnomAD4 genome

AF:

0.160

AC:

24314

AN:

152182

Hom.:

5811

Cov.:

AF XY:

0.153

AC XY:

11415

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.519

Gnomad4 AMR

AF:

0.0810

Gnomad4 ASJ

AF:

0.0107

Gnomad4 EAS

AF:

0.0156

Gnomad4 SAS

AF:

0.0104

Gnomad4 FIN

AF:

0.00330

Gnomad4 NFE

AF:

0.0148

Gnomad4 OTH

AF:

0.124

Alfa

AF:

0.100

Hom.:

416

Bravo

AF:

0.182

Asia WGS

AF:

0.0560

AC:

198

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

-0.91

CADD

Benign

DANN

Benign

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.20

Position offset: -39

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