Variant 18-68681335-T-C 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.906-225A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00703 in 611,580 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.022 ( 112 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 33 hom. )

Consequence

TMX3
NM_019022.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.411

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=-0.7).

BP6

Variant 18-68681335-T-C is Benign according to our data. Variant chr18-68681335-T-C is described in ClinVar as [Benign]. Clinvar id is 1265855.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0735 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.906-225A>G		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.906-225A>G	intron_variant	1	NM_019022.5	ENSP00000299608	P1	Q96JJ7-1
TMX3	ENST00000564631.5 linkuse as main transcript	c.*590-225A>G	intron_variant, NMD_transcript_variant	1		ENSP00000456587
TMX3	ENST00000566135.1 linkuse as main transcript		upstream_gene_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3320

AN:

152148

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0757

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00962

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.0120

GnomAD4 exome

AF:

0.00210

AC:

966

AN:

459314

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

404

AN XY:

222568

show subpopulations

Gnomad4 AFR exome

AF:

0.0806

Gnomad4 AMR exome

AF:

0.00510

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000309

Gnomad4 OTH exome

AF:

0.00590

GnomAD4 genome

AF:

0.0219

AC:

3332

AN:

152266

Hom.:

112

Cov.:

AF XY:

0.0211

AC XY:

1571

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0757

Gnomad4 AMR

AF:

0.00961

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.0241

Hom.:

Bravo

AF:

0.0252

Asia WGS

AF:

0.00694

AC:

AN:

3472

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 23, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

4.1

DANN

Benign

0.72

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