rs141046414

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152564.5(VPS13B):c.1700G>A(p.Gly567Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000672 in 1,613,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. G567G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00069 ( 0 hom. )

Consequence

VPS13B
NM_152564.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:14O:1

Conservation

PhyloP100: 2.15

Publications

8 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: Myriad Women’s Health, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Laboratory for Molecular Medicine, G2P, Orphanet

VPS13B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12260088).

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.1700G>A	p.Gly567Glu	missense	Exon 13 of 62	NP_060360.3
VPS13B	NM_152564.5	MANE Select	c.1700G>A	p.Gly567Glu	missense	Exon 13 of 62	NP_689777.3
VPS13B	NM_015243.3		c.1700G>A	p.Gly567Glu	missense	Exon 13 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.1700G>A	p.Gly567Glu	missense	Exon 13 of 62	ENSP00000351346.2	Q7Z7G8-1
VPS13B	ENST00000357162.7	TSL:1 MANE Select	c.1700G>A	p.Gly567Glu	missense	Exon 13 of 62	ENSP00000349685.2	Q7Z7G8-2
VPS13B	ENST00000355155.6	TSL:1	n.1700G>A		non_coding_transcript_exon	Exon 13 of 28	ENSP00000347281.2	A0A8C8KE22

Frequencies

GnomAD3 genomes

AF:

0.000513

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000911

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000379

AC:

AN:

250942

AF XY:

0.000420

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000869

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000758

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000688

AC:

1006

AN:

1461468

Hom.:

Cov.:

AF XY:

0.000653

AC XY:

475

AN XY:

726994

show subpopulations

African (AFR)

AF:

0.0000897

AC:

AN:

33456

American (AMR)

AF:

0.000112

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39652

South Asian (SAS)

AF:

0.00

AC:

AN:

86110

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000869

AC:

966

AN:

1111880

Other (OTH)

AF:

0.000530

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

114

170

227

284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

102

136

170

<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:

0.000512

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.000443

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41570

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000912

AC:

AN:

68014

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

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:

0.000771

Hom.:

Bravo

AF:

0.000472

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000362

AC:

EpiCase

AF:

0.000927

EpiControl

AF:

0.000771

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cohen syndrome (8)

not provided (3)

not specified (2)

Inborn genetic diseases (1)

VPS13B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.034

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.7

PhyloP100

2.1

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-2.0

REVEL

Benign

0.26

Sift

Benign

0.26

Sift4G

Uncertain

0.0080

Polyphen

0.091

Vest4

0.60

MVP

0.68

MPC

0.64

ClinPred

0.040

GERP RS

3.6

Varity_R

0.16

gMVP

0.56

Mutation Taster

=1/99

disease causing

(source)

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

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