Genetic Variant VPS51:p.Lys131Gln (chr11-65107613-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013265.4(VPS51):c.391A>C(p.Lys131Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000221 in 1,447,228 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 (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

VPS51
NM_013265.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.24

Publications

0 publications found

Variant links:

Genes affected

VPS51 (HGNC:1172): (VPS51 subunit of GARP complex) This gene encodes a member of the vacuolar protein sorting-associated protein 51 family. The encoded protein is a component of the Golgi-associated retrograde protein complex which acts as a tethering factor for carriers in retrograde transport from the early and late endosomes to the trans-Golgi network. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

VPS51 Gene-Disease associations (from GenCC):

pontocerebellar hypoplasia, type 13
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

VPS51 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18568441).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013265.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS51	NM_013265.4	MANE Select	c.391A>C	p.Lys131Gln	missense	Exon 3 of 10	NP_037397.2
	VPS51	NR_073519.2		n.428A>C		non_coding_transcript_exon	Exon 3 of 10

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VPS51	ENST00000279281.8	TSL:1 MANE Select	c.391A>C	p.Lys131Gln	missense	Exon 3 of 10	ENSP00000279281.3	Q9UID3-1
VPS51	ENST00000527646.5	TSL:1	n.66A>C		non_coding_transcript_exon	Exon 2 of 9
VPS51	ENST00000529180.1	TSL:3	c.391A>C	p.Lys131Gln	missense	Exon 3 of 4	ENSP00000435245.1	E9PKX7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000160

AC:

AN:

249860

AF XY:

0.0000222

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000221

AC:

AN:

1447228

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

716552

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33220

American (AMR)

AF:

0.00

AC:

AN:

44300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25954

East Asian (EAS)

AF:

0.00

AC:

AN:

39214

South Asian (SAS)

AF:

0.00

AC:

AN:

85830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.0000291

AC:

AN:

1100170

Other (OTH)

AF:

0.00

AC:

AN:

59632

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000313

Hom.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.026

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.058

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0060

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

5.2

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.4

REVEL

Benign

0.058

Sift

Benign

0.27

Sift4G

Benign

0.11

Polyphen

0.098

Vest4

0.44

MutPred

0.47

Loss of ubiquitination at K131 (P = 0.0103)

MVP

0.33

MPC

1.0

ClinPred

0.47

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.087

gMVP

0.52

Mutation Taster

=75/25

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over