6-32041812-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_001365276.2(TNXB):c.12592G>A(p.Ala4198Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 17)

Exomes 𝑓: 0.0016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TNXB
NM_001365276.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.81

Variant links:

Genes affected

TNXB (HGNC:11976): (tenascin XB) This gene encodes a member of the tenascin family of extracellular matrix glycoproteins. The tenascins have anti-adhesive effects, as opposed to fibronectin which is adhesive. This protein is thought to function in matrix maturation during wound healing, and its deficiency has been associated with the connective tissue disorder Ehlers-Danlos syndrome. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. It is one of four genes in this cluster which have been duplicated. The duplicated copy of this gene is incomplete and is a pseudogene which is transcribed but does not encode a protein. The structure of this gene is unusual in that it overlaps the CREBL1 and CYP21A2 genes at its 5' and 3' ends, respectively. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

TNXB links:

CYP21A2 (HGNC:2600): (cytochrome P450 family 21 subfamily A member 2) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and hydroxylates steroids at the 21 position. Its activity is required for the synthesis of steroid hormones including cortisol and aldosterone. Mutations in this gene cause congenital adrenal hyperplasia. A related pseudogene is located near this gene; gene conversion events involving the functional gene and the pseudogene are thought to account for many cases of steroid 21-hydroxylase deficiency. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CYP21A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01037395).

BP6

Variant 6-32041812-C-T is Benign according to our data. Variant chr6-32041812-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1193708.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.12592G>A	p.Ala4198Thr	missense_variant	Exon 43 of 44	ENST00000644971.2	NP_001352205.1
CYP21A2	NM_000500.9 link	c.*678C>T		downstream_gene_variant		ENST00000644719.2	NP_000491.4	P08686Q16874Q08AG9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 link	c.12592G>A	p.Ala4198Thr	missense_variant	Exon 43 of 44		NM_001365276.2	ENSP00000496448.1		P22105-3
CYP21A2	ENST00000644719.2 link	c.*678C>T		downstream_gene_variant			NM_000500.9	ENSP00000496625.1		Q16874

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

123022

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000474

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00253

Gnomad SAS

AF:

0.00990

Gnomad FIN

AF:

0.000120

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000452

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00233

AC:

307

AN:

131534

Hom.:

AF XY:

0.00309

AC XY:

218

AN XY:

70640

show subpopulations

Gnomad AFR exome

AF:

0.000149

Gnomad AMR exome

AF:

0.000258

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00119

Gnomad SAS exome

AF:

0.0122

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.000716

Gnomad OTH exome

AF:

0.000509

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00160

AC:

1325

AN:

825926

Hom.:

Cov.:

AF XY:

0.00205

AC XY:

869

AN XY:

423872

show subpopulations

Gnomad4 AFR exome

AF:

0.000301

Gnomad4 AMR exome

AF:

0.000350

Gnomad4 ASJ exome

AF:

0.0000482

Gnomad4 EAS exome

AF:

0.00117

Gnomad4 SAS exome

AF:

0.0122

Gnomad4 FIN exome

AF:

0.000247

Gnomad4 NFE exome

AF:

0.000627

Gnomad4 OTH exome

AF:

0.00175

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000698

AC:

AN:

123146

Hom.:

Cov.:

AF XY:

0.000863

AC XY:

AN XY:

59086

show subpopulations

Gnomad4 AFR

AF:

0.000472

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00254

Gnomad4 SAS

AF:

0.00990

Gnomad4 FIN

AF:

0.000120

Gnomad4 NFE

AF:

0.000452

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000960

Hom.:

ExAC

AF:

0.00339

AC:

253

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TNXB: BS1 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 20, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Ehlers-Danlos syndrome due to tenascin-X deficiency;C4014831:Vesicoureteral reflux 8

Benign:1

Apr 01, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Uncertain

0.044

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.030

.;.;.;.;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

.;D;D;T;T

MetaRNN

Benign

0.010

T;T;T;T;T

MetaSVM

Uncertain

-0.19

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.4

.;.;N;N;.

REVEL

Uncertain

0.40

Sift

Benign

0.040

.;.;D;T;.

Sift4G

Uncertain

0.0030

.;.;D;T;D

Vest4

0.57, 0.27

MVP

0.42

MPC

2.9

ClinPred

0.061

GERP RS

4.7

Varity_R

0.17

gMVP

0.36

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