6-32064966-G-C

Position:

• chr6-32064966-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001365276.2(TNXB):​c.6696C>G​(p.Asp2232Glu) 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. 15/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D2232D) 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: -4.29

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1178107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TNXB	NM_001365276.2	c.6696C>G	p.Asp2232Glu	missense_variant	19/44	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1	c.7437C>G	p.Asp2479Glu	missense_variant	20/45		NP_001415264.1
TNXB	NM_019105.8	c.6696C>G	p.Asp2232Glu	missense_variant	19/44		NP_061978.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TNXB	ENST00000644971.2	c.6696C>G	p.Asp2232Glu	missense_variant	19/44		NM_001365276.2	ENSP00000496448.1
TNXB	ENST00000647633.1	c.7437C>G	p.Asp2479Glu	missense_variant	20/45			ENSP00000497649.1
TNXB	ENST00000375244.7	c.6696C>G	p.Asp2232Glu	missense_variant	19/44	5		ENSP00000364393.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 69

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.0020
DANN	Benign	0.94
DEOGEN2	Benign	0.043	T;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0073	N
LIST_S2	Benign	0.21	.;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.96	T
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.4	.;.;N
REVEL	Benign	0.12
Sift	Benign	0.26	.;.;T
Sift4G	Uncertain	0.045	.;.;D
Vest4		0.15
MVP		0.15
ClinPred		0.74	D
GERP RS		-6.9
Varity_R		0.053

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: rs204883; hg19: chr6-32032743;