rs11423899

Positions:

• chr6-32042415-C-CT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001365276.2(TNXB):​c.12210+39_12210+40insA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0015 (976 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNXB NM_001365276.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.69

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 6-32042415-C-CT is Benign according to our data. Variant chr6-32042415-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 261121.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.12210+39_12210+40insA		intron_variant		ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8	c.12204+39_12204+40insA		intron_variant			NP_061978.6
TNXB	NM_032470.4	c.1497+39_1497+40insA		intron_variant			NP_115859.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.12210+39_12210+40insA		intron_variant			NM_001365276.2	ENSP00000496448

Frequencies

GnomAD3 genomes AF: 0.00 AC: 191 AN: 135452 Hom.: 0 Cov.: 20 FAILED QC

Gnomad AFR AF: 0.00313

Gnomad AMI AF: 0.00246

Gnomad AMR AF: 0.00161

Gnomad ASJ AF: 0.000620

Gnomad EAS AF: 0.000625

Gnomad SAS AF: 0.00197

Gnomad FIN AF: 0.0000990

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000716

Gnomad OTH AF: 0.00161

GnomAD3 exomes AF: 0.0000731 AC: 18 AN: 246348 Hom.: 8 AF XY: 0.000120 AC XY: 16 AN XY: 133234

Gnomad AFR exome AF: 0.000264

Gnomad AMR exome AF: 0.0000583

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000101

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000627

Gnomad OTH exome AF: 0.000331

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00147 AC: 2070 AN: 1405160 Hom.: 976 Cov.: 32 AF XY: 0.00184 AC XY: 1286 AN XY: 699232

Gnomad4 AFR exome AF: 0.00613

Gnomad4 AMR exome AF: 0.00175

Gnomad4 ASJ exome AF: 0.00229

Gnomad4 EAS exome AF: 0.000773

Gnomad4 SAS exome AF: 0.0113

Gnomad4 FIN exome AF: 0.000438

Gnomad4 NFE exome AF: 0.000672

Gnomad4 OTH exome AF: 0.00128

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00141 AC: 191 AN: 135568 Hom.: 0 Cov.: 20 AF XY: 0.00151 AC XY: 100 AN XY: 66076

Gnomad4 AFR AF: 0.00312

Gnomad4 AMR AF: 0.00161

Gnomad4 ASJ AF: 0.000620

Gnomad4 EAS AF: 0.000627

Gnomad4 SAS AF: 0.00197

Gnomad4 FIN AF: 0.0000990

Gnomad4 NFE AF: 0.000716

Gnomad4 OTH AF: 0.00160

Alfa AF: 0.000325 Hom.: 4

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs11423899; hg19: chr6-32010192;