GeneBe

rs567536854

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

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. 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
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TOP6BLNM_001302084.2 linkc.-118_-104delCGGCGGCGGCGGCGG 5_prime_UTR_variant Exon 1 of 15 ENST00000540737.7 NP_001289013.1 Q8N6T0B4DXL1
TOP6BLNM_024650.4 linkc.-59_-45delCGGCGGCGGCGGCGG 5_prime_UTR_variant Exon 1 of 17 NP_078926.4 Q8N6T0-4
SPTBN2XM_047427495.1 linkc.-498_-484delGCCGCCGCCGCCGCC upstream_gene_variant XP_047283451.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C11orf80ENST00000540737 linkc.-118_-104delCGGCGGCGGCGGCGG 5_prime_UTR_variant Exon 1 of 15 2 NM_001302084.2 ENSP00000444319.1 B4DXL1

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
Gnomad4 AFR exome
AF:
0.0000861
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00194
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000899
Gnomad4 OTH exome
AF:
0.000409
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
Gnomad4 AFR
AF:
0.0000981
Gnomad4 AMR
AF:
0.0000666
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00191
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000452
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs567536854; hg19: chr11-66512290; API