rs398124337

Variant summary

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

The NM_152564.5(VPS13B):​c.6455-5_6455-4delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,978 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

VPS13B
NM_152564.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.387
Variant links:
Genes affected
VPS13B (HGNC:2183): (vacuolar protein sorting 13 homolog B) This gene encodes a potential transmembrane protein that may function in vesicle-mediated transport and sorting of proteins within the cell. This protein may play a role in the development and the function of the eye, hematological system, and central nervous system. Mutations in this gene have been associated with Cohen syndrome. Multiple splice variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

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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
VPS13BNM_017890.5 linkc.6530-5_6530-4delTT splice_region_variant, intron_variant Intron 36 of 61 ENST00000358544.7 NP_060360.3 Q7Z7G8-1
VPS13BNM_152564.5 linkc.6455-5_6455-4delTT splice_region_variant, intron_variant Intron 36 of 61 ENST00000357162.7 NP_689777.3 Q7Z7G8-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VPS13BENST00000358544.7 linkc.6530-12_6530-11delTT intron_variant Intron 36 of 61 1 NM_017890.5 ENSP00000351346.2 Q7Z7G8-1
VPS13BENST00000357162.7 linkc.6455-12_6455-11delTT intron_variant Intron 36 of 61 1 NM_152564.5 ENSP00000349685.2 Q7Z7G8-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.03e-7
AC:
1
AN:
1422978
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
709192
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.27e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-100729386; API