chr6-32044149-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001365276.2(TNXB):​c.11264-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.019 in 1,471,384 control chromosomes in the GnomAD database, including 548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 56 hom., cov: 19)
Exomes 𝑓: 0.019 ( 492 hom. )

Consequence

TNXB
NM_001365276.2 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.64
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 6-32044149-C-T is Benign according to our data. Variant chr6-32044149-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 261104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0162 (2150/132592) while in subpopulation NFE AF= 0.0235 (1443/61452). AF 95% confidence interval is 0.0225. There are 56 homozygotes in gnomad4. There are 1059 alleles in male gnomad4 subpopulation. Median coverage is 19. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 56 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TNXBNM_001365276.2 linkuse as main transcriptc.11264-20G>A intron_variant ENST00000644971.2 NP_001352205.1
TNXBNM_019105.8 linkuse as main transcriptc.11258-20G>A intron_variant NP_061978.6
TNXBNM_032470.4 linkuse as main transcriptc.551-20G>A intron_variant NP_115859.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TNXBENST00000644971.2 linkuse as main transcriptc.11264-20G>A intron_variant NM_001365276.2 ENSP00000496448 P22105-3

Frequencies

GnomAD3 genomes
AF:
0.0163
AC:
2155
AN:
132510
Hom.:
57
Cov.:
19
show subpopulations
Gnomad AFR
AF:
0.00318
Gnomad AMI
AF:
0.0151
Gnomad AMR
AF:
0.00537
Gnomad ASJ
AF:
0.0194
Gnomad EAS
AF:
0.0195
Gnomad SAS
AF:
0.0132
Gnomad FIN
AF:
0.0315
Gnomad MID
AF:
0.0304
Gnomad NFE
AF:
0.0235
Gnomad OTH
AF:
0.0139
GnomAD3 exomes
AF:
0.0185
AC:
3726
AN:
201420
Hom.:
108
AF XY:
0.0187
AC XY:
2039
AN XY:
109078
show subpopulations
Gnomad AFR exome
AF:
0.00287
Gnomad AMR exome
AF:
0.00922
Gnomad ASJ exome
AF:
0.0197
Gnomad EAS exome
AF:
0.0216
Gnomad SAS exome
AF:
0.0153
Gnomad FIN exome
AF:
0.0295
Gnomad NFE exome
AF:
0.0216
Gnomad OTH exome
AF:
0.0214
GnomAD4 exome
AF:
0.0192
AC:
25760
AN:
1338792
Hom.:
492
Cov.:
31
AF XY:
0.0192
AC XY:
12779
AN XY:
665472
show subpopulations
Gnomad4 AFR exome
AF:
0.00261
Gnomad4 AMR exome
AF:
0.00919
Gnomad4 ASJ exome
AF:
0.0197
Gnomad4 EAS exome
AF:
0.0123
Gnomad4 SAS exome
AF:
0.0147
Gnomad4 FIN exome
AF:
0.0288
Gnomad4 NFE exome
AF:
0.0204
Gnomad4 OTH exome
AF:
0.0170
GnomAD4 genome
AF:
0.0162
AC:
2150
AN:
132592
Hom.:
56
Cov.:
19
AF XY:
0.0165
AC XY:
1059
AN XY:
64068
show subpopulations
Gnomad4 AFR
AF:
0.00317
Gnomad4 AMR
AF:
0.00529
Gnomad4 ASJ
AF:
0.0194
Gnomad4 EAS
AF:
0.0195
Gnomad4 SAS
AF:
0.0130
Gnomad4 FIN
AF:
0.0315
Gnomad4 NFE
AF:
0.0235
Gnomad4 OTH
AF:
0.0138
Alfa
AF:
0.0214
Hom.:
22
Bravo
AF:
0.0141

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:1
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
0.020
DANN
Benign
0.56

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs77466839; hg19: chr6-32011926; API