Variant 6-32042688-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001365276.2(TNXB):c.12058+11G>A variant causes a intron 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 0.011 ( 13 hom., cov: 15)

Exomes 𝑓: 0.016 ( 211 hom. )

Consequence

TNXB
NM_001365276.2 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.73

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:

TNXB (HGNC:):

TNXB 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=-0.92).

BP6

Variant 6-32042688-C-T is Benign according to our data. Variant chr6-32042688-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 261118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0113 (1332/117466) while in subpopulation NFE AF= 0.0182 (1012/55542). AF 95% confidence interval is 0.0173. There are 13 homozygotes in gnomad4. There are 608 alleles in male gnomad4 subpopulation. Median coverage is 15. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
TNXB	NM_001365276.2 linkuse as main transcript	c.12058+11G>A	intron_variant	ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8 linkuse as main transcript	c.12052+11G>A	intron_variant		NP_061978.6	P22105-1O95680Q9Y464O95681
TNXB	NM_032470.4 linkuse as main transcript	c.1345+11G>A	intron_variant		NP_115859.2	P22105-2Q6IPK3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2 linkuse as main transcript	c.12058+11G>A		intron_variant			NM_001365276.2	ENSP00000496448.1		P22105-3

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1332

AN:

117350

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00174

Gnomad ASJ

AF:

0.00101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000314

Gnomad FIN

AF:

0.0263

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0182

Gnomad OTH

AF:

0.00484

GnomAD3 exomes

AF:

0.0102

AC:

1351

AN:

133078

Hom.:

AF XY:

0.0102

AC XY:

739

AN XY:

72356

show subpopulations

Gnomad AFR exome

AF:

0.00233

Gnomad AMR exome

AF:

0.00173

Gnomad ASJ exome

AF:

0.000752

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000897

Gnomad FIN exome

AF:

0.0262

Gnomad NFE exome

AF:

0.0214

Gnomad OTH exome

AF:

0.00641

GnomAD4 exome

AF:

0.0159

AC:

17226

AN:

1086778

Hom.:

211

Cov.:

AF XY:

0.0153

AC XY:

8365

AN XY:

546304

show subpopulations

Gnomad4 AFR exome

AF:

0.00216

Gnomad4 AMR exome

AF:

0.00160

Gnomad4 ASJ exome

AF:

0.000908

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000402

Gnomad4 FIN exome

AF:

0.0316

Gnomad4 NFE exome

AF:

0.0192

Gnomad4 OTH exome

AF:

0.00999

GnomAD4 genome

AF:

0.0113

AC:

1332

AN:

117466

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

608

AN XY:

56140

show subpopulations

Gnomad4 AFR

AF:

0.00269

Gnomad4 AMR

AF:

0.00174

Gnomad4 ASJ

AF:

0.00101

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000314

Gnomad4 FIN

AF:

0.0263

Gnomad4 NFE

AF:

0.0182

Gnomad4 OTH

AF:

0.00476

Alfa

AF:

0.00658

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.077

DANN

Benign

0.80

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