Variant 6-32041679-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_001365276.2(TNXB):c.12633+92T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,112,634 control chromosomes in the GnomAD database, including 32,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.25 ( 6009 hom., cov: 23)

Exomes 𝑓: 0.15 ( 26531 hom. )

Consequence

TNXB
NM_001365276.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.390

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:

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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=-0.95).

BP6

Variant 6-32041679-A-G is Benign according to our data. Variant chr6-32041679-A-G is described in ClinVar as [Benign]. Clinvar id is 1284242.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-32041679-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.12633+92T>C		intron_variant		ENST00000644971.2	NP_001352205.1
CYP21A2	NM_000500.9 link	c.*545A>G		downstream_gene_variant		ENST00000644719.2	NP_000491.4	P08686Q16874Q08AG9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 link	c.12633+92T>C		intron_variant			NM_001365276.2	ENSP00000496448.1		P22105-3
CYP21A2	ENST00000644719.2 link	c.*545A>G		downstream_gene_variant			NM_000500.9	ENSP00000496625.1		Q16874

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

35469

AN:

142214

Hom.:

6000

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0686

Gnomad AMI

AF:

0.416

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.454

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.363

Gnomad MID

AF:

0.319

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.239

GnomAD4 exome

AF:

0.146

AC:

142125

AN:

970316

Hom.:

26531

Cov.:

AF XY:

0.153

AC XY:

75147

AN XY:

490408

show subpopulations

Gnomad4 AFR exome

AF:

0.0294

Gnomad4 AMR exome

AF:

0.244

Gnomad4 ASJ exome

AF:

0.285

Gnomad4 EAS exome

AF:

0.225

Gnomad4 SAS exome

AF:

0.169

Gnomad4 FIN exome

AF:

0.293

Gnomad4 NFE exome

AF:

0.126

Gnomad4 OTH exome

AF:

0.172

GnomAD4 genome

AF:

0.249

AC:

35492

AN:

142318

Hom.:

6009

Cov.:

AF XY:

0.253

AC XY:

17501

AN XY:

69146

show subpopulations

Gnomad4 AFR

AF:

0.0686

Gnomad4 AMR

AF:

0.362

Gnomad4 ASJ

AF:

0.454

Gnomad4 EAS

AF:

0.188

Gnomad4 SAS

AF:

0.244

Gnomad4 FIN

AF:

0.363

Gnomad4 NFE

AF:

0.311

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.293

Hom.:

847

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

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.11

DANN

Benign

0.37

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