rs150783688

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_152564.5(VPS13B):c.1463C>T(p.Thr488Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000398 in 1,613,088 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T488T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 1 hom. )

Consequence

VPS13B
NM_152564.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:7

Conservation

PhyloP100: 0.275

Publications

5 publications found

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]

VPS13B Gene-Disease associations (from GenCC):

Cohen syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Myriad Women’s Health, Laboratory for Molecular Medicine, Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp

VPS13B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008333594).

BP6

Variant 8-99135633-C-T is Benign according to our data. Variant chr8-99135633-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 95832.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152564.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
VPS13B	NM_017890.5	MANE Plus Clinical	c.1463C>T	p.Thr488Met	missense	Exon 11 of 62	NP_060360.3
VPS13B	NM_152564.5	MANE Select	c.1463C>T	p.Thr488Met	missense	Exon 11 of 62	NP_689777.3
VPS13B	NM_015243.3		c.1463C>T	p.Thr488Met	missense	Exon 11 of 18	NP_056058.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VPS13B	ENST00000358544.7	TSL:1 MANE Plus Clinical	c.1463C>T	p.Thr488Met	missense	Exon 11 of 62	ENSP00000351346.2	Q7Z7G8-1
VPS13B	ENST00000357162.7	TSL:1 MANE Select	c.1463C>T	p.Thr488Met	missense	Exon 11 of 62	ENSP00000349685.2	Q7Z7G8-2
VPS13B	ENST00000355155.6	TSL:1	n.1463C>T		non_coding_transcript_exon	Exon 11 of 28	ENSP00000347281.2	A0A8C8KE22

Frequencies

GnomAD3 genomes

AF:

0.000454

AC:

AN:

151930

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000427

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000562

AC:

141

AN:

250992

AF XY:

0.000590

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00735

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000494

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000392

AC:

573

AN:

1461158

Hom.:

Cov.:

AF XY:

0.000392

AC XY:

285

AN XY:

726862

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.0000448

AC:

AN:

44690

Ashkenazi Jewish (ASJ)

AF:

0.00915

AC:

239

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39618

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86222

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000246

AC:

273

AN:

1111566

Other (OTH)

AF:

0.000895

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

120

150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000454

AC:

AN:

151930

Hom.:

Cov.:

AF XY:

0.000310

AC XY:

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000427

AC:

AN:

67924

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000689

Hom.:

Bravo

AF:

0.000450

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000535

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cohen syndrome (4)

not provided (4)

Inborn genetic diseases (1)

not specified (1)

VPS13B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.092

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.058

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.028

MetaRNN

Benign

0.0083

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.55

PhyloP100

0.28

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.9

REVEL

Benign

0.070

Sift

Benign

0.11

Sift4G

Uncertain

0.045

Polyphen

0.0070

Vest4

0.17

MVP

0.65

MPC

0.14

ClinPred

0.012

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.028

gMVP

0.21

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over