rs1009382

Positions:

• chr6-32058330-C-A
• chr6-32058330-C-G
• chr6-32058330-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001365276.2(TNXB):​c.7553G>T​(p.Gly2518Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. 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. G2518E) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TNXB NM_001365276.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350

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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05685523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.7553G>T	p.Gly2518Val	missense_variant	22/44	ENST00000644971.2	NP_001352205.1
TNXB	NM_019105.8	c.7553G>T	p.Gly2518Val	missense_variant	22/44		NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.7553G>T	p.Gly2518Val	missense_variant	22/44		NM_001365276.2	ENSP00000496448
TNXB	ENST00000647633.1	c.8294G>T	p.Gly2765Val	missense_variant	23/45			ENSP00000497649	P1
TNXB	ENST00000375244.7	c.7553G>T	p.Gly2518Val	missense_variant	22/44	5		ENSP00000364393

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 65

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.4
DANN	Benign	0.73
DEOGEN2	Benign	0.065	T;.;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.11	.;T;T;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.057	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.34	.;.;N;.
REVEL	Benign	0.014
Sift	Benign	0.038	.;.;D;.
Sift4G	Uncertain	0.0060	.;.;D;T
Vest4		0.085
MVP		0.043
ClinPred		0.12	T
GERP RS		3.3
Varity_R		0.042

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: rs1009382; hg19: chr6-32026107;