dbSNP rs529527925: TNXB:p.Ala3349Ser (chr6-32048363-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001365276.2(TNXB):c.10045G>T(p.Ala3349Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000378 in 1,322,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/19 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000038 ( 0 hom. )

Consequence

TNXB
NM_001365276.2 missense, splice_region

Scores

Splicing: ADA: 0.8829

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.330

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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=0.07977235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNXB	NM_001365276.2 link	c.10045G>T	p.Ala3349Ser	missense_variant, splice_region_variant	Exon 29 of 44	ENST00000644971.2	NP_001352205.1
TNXB	NM_001428335.1 link	c.10786G>T	p.Ala3596Ser	missense_variant, splice_region_variant	Exon 30 of 45		NP_001415264.1
TNXB	NM_019105.8 link	c.10039G>T	p.Ala3347Ser	missense_variant, splice_region_variant	Exon 29 of 44		NP_061978.6	P22105-1O95680Q9Y464O95681

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TNXB	ENST00000644971.2 link	c.10045G>T	p.Ala3349Ser	missense_variant, splice_region_variant	Exon 29 of 44		NM_001365276.2	ENSP00000496448.1	P22105-3
TNXB	ENST00000647633.1 link	c.10786G>T	p.Ala3596Ser	missense_variant, splice_region_variant	Exon 30 of 45			ENSP00000497649.1	A0A3B3ISX9
TNXB	ENST00000375244.7 link	c.10045G>T	p.Ala3349Ser	missense_variant, splice_region_variant	Exon 29 of 44	5		ENSP00000364393.3	P22105-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000378

AC:

AN:

1322560

Hom.:

Cov.:

AF XY:

0.00000466

AC XY:

AN XY:

643782

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000480

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.8

DANN

Benign

0.92

DEOGEN2

Benign

0.019

.;.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.087

.;T;T;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.080

T;T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.5

.;.;N;.

REVEL

Benign

0.044

Sift

Benign

0.078

.;.;T;.

Sift4G

Benign

0.36

.;.;T;T

Vest4

0.076

MVP

0.082

ClinPred

0.14

GERP RS

-1.8

Varity_R

0.069

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.88

dbscSNV1_RF

Benign

0.65

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over