Variant 11-65096451-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_013265.4(VPS51):c.201C>G(p.His67Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000945 in 1,439,550 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000095 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

VPS51
NM_013265.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.93

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 links:

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=0.14011073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS51	NM_013265.4 linkuse as main transcript	c.201C>G	p.His67Gln	missense_variant	1/10	ENST00000279281.8	NP_037397.2
VPS51	NR_073519.2 linkuse as main transcript	n.238C>G		non_coding_transcript_exon_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS51	ENST00000279281.8 linkuse as main transcript	c.201C>G	p.His67Gln	missense_variant	1/10	1	NM_013265.4	ENSP00000279281	P1	Q9UID3-1

Frequencies

GnomAD3 genomes

AF:

0.0000950

AC:

AN:

147428

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000248

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000878

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000135

Gnomad OTH

AF:

0.000485

GnomAD3 exomes

AF:

0.0000690

AC:

AN:

159434

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

90012

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000913

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000687

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000944

AC:

122

AN:

1292122

Hom.:

Cov.:

AF XY:

0.0000908

AC XY:

AN XY:

638788

show subpopulations

Gnomad4 AFR exome

AF:

0.0000377

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000969

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000131

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000961

Gnomad4 OTH exome

AF:

0.0000599

GnomAD4 genome

AF:

0.0000950

AC:

AN:

147428

Hom.:

Cov.:

AF XY:

0.0000975

AC XY:

AN XY:

71818

show subpopulations

Gnomad4 AFR

AF:

0.0000248

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000878

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000135

Gnomad4 OTH

AF:

0.000485

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000764

AC:

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 submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.201C>G (p.H67Q) alteration is located in exon 1 (coding exon 1) of the VPS51 gene. This alteration results from a C to G substitution at nucleotide position 201, causing the histidine (H) at amino acid position 67 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Uncertain

0.072

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.087

T;T;T;T;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.071

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.81

T;T;T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.14

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.8

.;.;L;.;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-4.0

D;D;N;D;.

REVEL

Benign

0.16

Sift

Benign

0.11

T;T;T;T;.

Sift4G

Uncertain

0.018

D;D;T;D;.

Polyphen

0.74

.;.;P;.;.

Vest4

0.56

MutPred

0.46

.;Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);Loss of helix (P = 0.0033);

MVP

0.33

MPC

1.3

ClinPred

0.30

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.27

gMVP

0.32

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over