rs61740712
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001365276.2(TNXB):c.8601C>T(p.Pro2867=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00982 in 1,613,638 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0086 ( 5 hom., cov: 32)
Exomes 𝑓: 0.0099 ( 79 hom. )
Consequence
TNXB
NM_001365276.2 synonymous
NM_001365276.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.39
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 Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
Variant 6-32053578-G-A is Benign according to our data. Variant chr6-32053578-G-A is described in ClinVar as [Benign]. Clinvar id is 261170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-32053578-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-3.39 with no splicing effect.
BS2
?
High Homozygotes in GnomAd4 at 5 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNXB | NM_001365276.2 | c.8601C>T | p.Pro2867= | synonymous_variant | 25/44 | ENST00000644971.2 | |
TNXB | NM_019105.8 | c.8595C>T | p.Pro2865= | synonymous_variant | 25/44 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNXB | ENST00000644971.2 | c.8601C>T | p.Pro2867= | synonymous_variant | 25/44 | NM_001365276.2 | |||
TNXB | ENST00000647633.1 | c.9342C>T | p.Pro3114= | synonymous_variant | 26/45 | P1 | |||
TNXB | ENST00000375244.7 | c.8601C>T | p.Pro2867= | synonymous_variant | 25/44 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00862 AC: 1311AN: 152144Hom.: 5 Cov.: 32
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GnomAD3 exomes AF: 0.00859 AC: 2121AN: 246948Hom.: 13 AF XY: 0.00902 AC XY: 1213AN XY: 134438
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GnomAD4 exome AF: 0.00995 AC: 14535AN: 1461376Hom.: 79 Cov.: 33 AF XY: 0.0101 AC XY: 7335AN XY: 726982
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GnomAD4 genome ? AF: 0.00860 AC: 1309AN: 152262Hom.: 5 Cov.: 32 AF XY: 0.00884 AC XY: 658AN XY: 74438
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | TNXB: BP4, BP7, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 19, 2019 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Ehlers-Danlos syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jun 02, 2022 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 08, 2019 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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