rs1554567542

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017890.5(VPS13B):​c.8833C>T​(p.Pro2945Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P2945P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

VPS13B
NM_017890.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1331205).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
VPS13BNM_017890.5 linkuse as main transcriptc.8833C>T p.Pro2945Ser missense_variant 48/62 ENST00000358544.7
VPS13BNM_152564.5 linkuse as main transcriptc.8758C>T p.Pro2920Ser missense_variant 48/62 ENST00000357162.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
VPS13BENST00000358544.7 linkuse as main transcriptc.8833C>T p.Pro2945Ser missense_variant 48/621 NM_017890.5 Q7Z7G8-1
VPS13BENST00000357162.7 linkuse as main transcriptc.8758C>T p.Pro2920Ser missense_variant 48/621 NM_152564.5 P1Q7Z7G8-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461544
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727062
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:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAthena DiagnosticsMar 06, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.093
BayesDel_addAF
Benign
-0.096
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
15
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
.;T
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.38
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.74
T;T
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
1.4
.;L
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-2.0
N;N
REVEL
Benign
0.072
Sift
Benign
0.082
T;T
Sift4G
Benign
0.16
T;T
Polyphen
0.037
B;B
Vest4
0.32
MutPred
0.46
.;Loss of loop (P = 0.0128);
MVP
0.68
MPC
0.13
ClinPred
0.32
T
GERP RS
4.1
Varity_R
0.056
gMVP
0.48

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: rs1554567542; hg19: chr8-100831776; API