6-32097988-C-T

Variant names:

• chr6-32097988-C-T
• NM_001365276.2:c.211G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001365276.2(TNXB):​c.211G>A​(p.Val71Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,002 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V71L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TNXB NM_001365276.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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]

ENSG00000284829 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.211G>A	p.Val71Met	missense_variant	Exon 2 of 44	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1	c.211G>A	p.Val71Met	missense_variant	Exon 2 of 45		NP_001415264.1
TNXB	NM_019105.8	c.211G>A	p.Val71Met	missense_variant	Exon 2 of 44		NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.211G>A	p.Val71Met	missense_variant	Exon 2 of 44		NM_001365276.2	ENSP00000496448.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455002 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 723406

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;.;T;.;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.93	.;D;D;D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.45	T;T;T;T;T
MetaSVM	Uncertain	0.58	D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-2.0	.;.;N;.;N
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	.;.;D;.;D
Sift4G	Pathogenic	0.0010	.;.;D;D;D
Vest4		0.37, 0.48
MutPred		0.33		Gain of ubiquitination at K69 (P = 0.0964);Gain of ubiquitination at K69 (P = 0.0964);Gain of ubiquitination at K69 (P = 0.0964);Gain of ubiquitination at K69 (P = 0.0964);Gain of ubiquitination at K69 (P = 0.0964);
MVP		0.34
ClinPred		0.99	D
GERP RS		4.6
Varity_R		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-32065765;