rs204886

Variant names:

• chr6-32061638-T-C
• rs204886
• NM_001365276.2:c.7251A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-32061638-T-C
• chr6-32061638-T-A
• chr6-32061638-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001365276.2(TNXB):​c.7251A>G​(p.Leu2417Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,612,278 control chromosomes in the GnomAD database, including 248,315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (23052 hom., cov: 30)
  • Exomes 𝑓: 0.55 (225263 hom.)
• Consequence: TNXB NM_001365276.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.472
• Publications: 15 publications found

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 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• Ehlers-Danlos syndrome due to tenascin-X deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Illumina, Genomics England PanelApp, PanelApp Australia
• familial vesicoureteral reflux

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• vesicoureteral reflux 8

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 6-32061638-T-C is Benign according to our data. Variant chr6-32061638-T-C is described in ClinVar as Benign. ClinVar VariationId is 261156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.472 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365276.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNXB	NM_001365276.2	MANE Select	c.7251A>G	p.Leu2417Leu	synonymous	Exon 21 of 44	NP_001352205.1	P22105-3
	TNXB	NM_001428335.1		c.7992A>G	p.Leu2664Leu	synonymous	Exon 22 of 45	NP_001415264.1	A0A3B3ISX9
	TNXB	NM_019105.8		c.7251A>G	p.Leu2417Leu	synonymous	Exon 21 of 44	NP_061978.6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TNXB	ENST00000644971.2	MANE Select	c.7251A>G	p.Leu2417Leu	synonymous	Exon 21 of 44	ENSP00000496448.1	P22105-3
	TNXB	ENST00000647633.1		c.7992A>G	p.Leu2664Leu	synonymous	Exon 22 of 45	ENSP00000497649.1	A0A3B3ISX9
	TNXB	ENST00000375244.7	TSL:5	c.7251A>G	p.Leu2417Leu	synonymous	Exon 21 of 44	ENSP00000364393.3	P22105-3

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82731 AN: 151648 Hom.: 23040 Cov.: 30

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.576

GnomAD2 exomes AF: 0.601 AC: 147134 AN: 244634 AF XY: 0.610

Gnomad AFR exome AF: 0.471

Gnomad AMR exome AF: 0.678

Gnomad ASJ exome AF: 0.686

Gnomad EAS exome AF: 0.601

Gnomad FIN exome AF: 0.557

Gnomad NFE exome AF: 0.554

Gnomad OTH exome AF: 0.585

GnomAD4 exome AF: 0.550 AC: 802625 AN: 1460512 Hom.: 225263 Cov.: 98 AF XY: 0.557 AC XY: 404837 AN XY: 726532

African (AFR) AF: 0.483 AC: 16158 AN: 33470

American (AMR) AF: 0.673 AC: 30108 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 17736 AN: 26132

East Asian (EAS) AF: 0.636 AC: 25236 AN: 39700

South Asian (SAS) AF: 0.748 AC: 64500 AN: 86248

European-Finnish (FIN) AF: 0.553 AC: 28956 AN: 52338

Middle Eastern (MID) AF: 0.691 AC: 3967 AN: 5740

European-Non Finnish (NFE) AF: 0.524 AC: 582258 AN: 1111814

Other (OTH) AF: 0.559 AC: 33706 AN: 60348

GnomAD4 genome AF: 0.546 AC: 82790 AN: 151766 Hom.: 23052 Cov.: 30 AF XY: 0.554 AC XY: 41069 AN XY: 74170

African (AFR) AF: 0.472 AC: 19535 AN: 41344

American (AMR) AF: 0.625 AC: 9534 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2370 AN: 3472

East Asian (EAS) AF: 0.618 AC: 3172 AN: 5134

South Asian (SAS) AF: 0.717 AC: 3443 AN: 4804

European-Finnish (FIN) AF: 0.563 AC: 5940 AN: 10560

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.542 AC: 36812 AN: 67886

Other (OTH) AF: 0.574 AC: 1207 AN: 2104

Alfa AF: 0.529 Hom.: 8511

Bravo AF: 0.545

EpiCase AF: 0.572

EpiControl AF: 0.579

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cardiovascular phenotype (1)
-	-	1	Ehlers-Danlos syndrome due to tenascin-X deficiency (1)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Vesicoureteral reflux 8 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.4
DANN	Benign	0.82
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs204886; hg19: chr6-32029415; COSMIC: COSV64472594; COSMIC: COSV64472594;