6-32041793-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong
The NM_001365276.2(TNXB):āc.12611A>Gā(p.Tyr4204Cys) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 18)
Exomes š: 0.0000024 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TNXB
NM_001365276.2 missense
NM_001365276.2 missense
Scores
13
3
2
Clinical Significance
Conservation
PhyloP100: 5.13
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.941
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TNXB | NM_001365276.2 | c.12611A>G | p.Tyr4204Cys | missense_variant | 43/44 | ENST00000644971.2 | NP_001352205.1 | |
TNXB | NM_001428335.1 | c.13352A>G | p.Tyr4451Cys | missense_variant | 44/45 | NP_001415264.1 | ||
TNXB | NM_019105.8 | c.12605A>G | p.Tyr4202Cys | missense_variant | 43/44 | NP_061978.6 | ||
TNXB | NM_032470.4 | c.1898A>G | p.Tyr633Cys | missense_variant | 12/13 | NP_115859.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 18
GnomAD3 genomes
Cov.:
18
GnomAD3 exomes AF: 0.00000776 AC: 1AN: 128790Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 69094
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000237 AC: 2AN: 842376Hom.: 0 Cov.: 12 AF XY: 0.00000231 AC XY: 1AN XY: 433038
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome Cov.: 18
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18
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 31, 2024 | The c.12605A>G (p.Y4202C) alteration is located in exon 43 (coding exon 42) of the TNXB gene. This alteration results from a A to G substitution at nucleotide position 12605, causing the tyrosine (Y) at amino acid position 4202 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;.;.;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Pathogenic
D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
.;.;D;D;.
REVEL
Pathogenic
Sift
Pathogenic
.;.;D;D;.
Sift4G
Uncertain
.;.;D;D;D
Vest4
0.78, 0.79
MVP
0.83
MPC
3.4
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at