GeneBe

rs567536854

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001302084.2(TOP6BL):​c.-118_-104delCGGCGGCGGCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,230,582 control chromosomes in the GnomAD database, including 1 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

TOP6BL
NM_001302084.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

4 publications found
Variant links:
Genes affected
TOP6BL (HGNC:26197): (TOP6B like initiator of meiotic double strand breaks) Predicted to be involved in meiotic DNA double-strand break formation and reciprocal meiotic recombination. Predicted to be located in chromosome. Implicated in gestational trophoblastic neoplasm. [provided by Alliance of Genome Resources, Apr 2022]
SPTBN2 (HGNC:11276): (spectrin beta, non-erythrocytic 2) Spectrins are principle components of a cell's membrane-cytoskeleton and are composed of two alpha and two beta spectrin subunits. The protein encoded by this gene (SPTBN2), is called spectrin beta non-erythrocytic 2 or beta-III spectrin. It is related to, but distinct from, the beta-II spectrin gene which is also known as spectrin beta non-erythrocytic 1 (SPTBN1). SPTBN2 regulates the glutamate signaling pathway by stabilizing the glutamate transporter EAAT4 at the surface of the plasma membrane. Mutations in this gene cause a form of spinocerebellar ataxia, SCA5, that is characterized by neurodegeneration, progressive locomotor incoordination, dysarthria, and uncoordinated eye movements. [provided by RefSeq, Dec 2009]
SPTBN2 Gene-Disease associations (from GenCC):
  • spinocerebellar ataxia type 5
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, ClinGen, G2P, Orphanet, Labcorp Genetics (formerly Invitae), Illumina
  • autosomal recessive spinocerebellar ataxia 14
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001302084.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TOP6BL
NM_001302084.2
MANE Select
c.-118_-104delCGGCGGCGGCGGCGG
5_prime_UTR
Exon 1 of 15NP_001289013.1Q8N6T0-6
TOP6BL
NM_024650.4
c.-59_-45delCGGCGGCGGCGGCGG
5_prime_UTR
Exon 1 of 17NP_078926.4

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TOP6BL
ENST00000540737.7
TSL:2 MANE Select
c.-118_-104delCGGCGGCGGCGGCGG
5_prime_UTR
Exon 1 of 15ENSP00000444319.1Q8N6T0-6
TOP6BL
ENST00000525908.6
TSL:2
c.-59_-45delCGGCGGCGGCGGCGG
5_prime_UTR
Exon 1 of 17ENSP00000432039.3A0A2U3TZP7
TOP6BL
ENST00000901160.1
c.-118_-104delCGGCGGCGGCGGCGG
5_prime_UTR
Exon 1 of 15ENSP00000571219.1

Frequencies

GnomAD3 genomes
AF:
0.000121
AC:
18
AN:
148182
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.0000983
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000667
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00212
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000452
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000150
AC:
162
AN:
1082298
Hom.:
1
AF XY:
0.000141
AC XY:
74
AN XY:
523458
show subpopulations
African (AFR)
AF:
0.0000861
AC:
2
AN:
23218
American (AMR)
AF:
0.00
AC:
0
AN:
11748
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
15594
East Asian (EAS)
AF:
0.00
AC:
0
AN:
26300
South Asian (SAS)
AF:
0.00194
AC:
61
AN:
31496
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
25362
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3764
European-Non Finnish (NFE)
AF:
0.0000899
AC:
81
AN:
900812
Other (OTH)
AF:
0.000409
AC:
18
AN:
44004
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.541
Heterozygous variant carriers
0
7
13
20
26
33
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000115
AC:
17
AN:
148284
Hom.:
0
Cov.:
0
AF XY:
0.000166
AC XY:
12
AN XY:
72246
show subpopulations
African (AFR)
AF:
0.0000981
AC:
4
AN:
40786
American (AMR)
AF:
0.0000666
AC:
1
AN:
15016
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3424
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4900
South Asian (SAS)
AF:
0.00191
AC:
9
AN:
4706
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
9840
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
290
European-Non Finnish (NFE)
AF:
0.0000452
AC:
3
AN:
66368
Other (OTH)
AF:
0.00
AC:
0
AN:
2060
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.467
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
682

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.0
Mutation Taster
=196/4
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs567536854; hg19: chr11-66512290; API