rs199757950

chr6-32045256-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001365276.2(TNXB):c.10677A>G(p.Leu3559=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00417 in 149,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0052 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNXB NM_001365276.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0250

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 Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 6-32045256-T-C is Benign according to our data. Variant chr6-32045256-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 261097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32045256-T-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.025 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TNXB	NM_001365276.2	c.10677A>G	p.Leu3559=	synonymous_variant	32/44	ENST00000644971.2
TNXB	NM_019105.8	c.10671A>G	p.Leu3557=	synonymous_variant	32/44
TNXB	NM_032470.4	c.-37A>G		5_prime_UTR_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TNXB	ENST00000644971.2	c.10677A>G	p.Leu3559=	synonymous_variant	32/44		NM_001365276.2

Frequencies

GnomAD3 genomes AF: 0.00422 AC: 630 AN: 149466 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00493

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.00120

Gnomad SAS AF: 0.00830

Gnomad FIN AF: 0.000381

Gnomad MID AF: 0.0667

Gnomad NFE AF: 0.00518

Gnomad OTH AF: 0.0133

GnomAD3 exomes AF: 0.00564 AC: 1135 AN: 201068 Hom.: 0 AF XY: 0.00641 AC XY: 705 AN XY: 110062

Gnomad AFR exome AF: 0.00198

Gnomad AMR exome AF: 0.00387

Gnomad ASJ exome AF: 0.0108

Gnomad EAS exome AF: 0.000375

Gnomad SAS exome AF: 0.0133

Gnomad FIN exome AF: 0.000327

Gnomad NFE exome AF: 0.00583

Gnomad OTH exome AF: 0.00862

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00518 AC: 7455 AN: 1439300 Hom.: 0 Cov.: 31 AF XY: 0.00547 AC XY: 3909 AN XY: 714498

Gnomad4 AFR exome AF: 0.00190

Gnomad4 AMR exome AF: 0.00383

Gnomad4 ASJ exome AF: 0.0112

Gnomad4 EAS exome AF: 0.000456

Gnomad4 SAS exome AF: 0.0111

Gnomad4 FIN exome AF: 0.000655

Gnomad4 NFE exome AF: 0.00484

Gnomad4 OTH exome AF: 0.00694

GnomAD4 genome AF: 0.00417 AC: 624 AN: 149586 Hom.: 0 Cov.: 20 AF XY: 0.00425 AC XY: 310 AN XY: 72942

Gnomad4 AFR AF: 0.00178

Gnomad4 AMR AF: 0.00493

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.00120

Gnomad4 SAS AF: 0.00810

Gnomad4 FIN AF: 0.000381

Gnomad4 NFE AF: 0.00518

Gnomad4 OTH AF: 0.0127

Alfa AF: 0.00936 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

TNXB: BP4, BP7, BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	5.4
Dann	Benign	0.81

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

Other links and lift over

dbSNP: rs199757950; hg19: chr6-32013033;