rs143165732

Variant summary

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

The NM_006052.2(VPS26C):ā€‹c.625G>Cā€‹(p.Val209Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000333 in 1,612,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.00017 ( 0 hom., cov: 33)
Exomes š‘“: 0.00035 ( 0 hom. )

Consequence

VPS26C
NM_006052.2 missense

Scores

2
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.43
Variant links:
Genes affected
VPS26C (HGNC:3044): (VPS26 endosomal protein sorting factor C) The region of chromosome 21 between genes CBR and ERG (CBR-ERG region), which spans 2.5 Mb on 21q22.2, has been defined by analysis of patients with partial trisomy 21. It contributes significantly to the pathogenesis of many characteristics of Down syndrome, including morphological features, hypotonia, and cognitive disability. The DSCR3 (Down syndrome critical region gene 3) gene is found in this region and is predictated to contain eight exons. DSCR3 is expressed in most tissues examined. [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=0.14285198).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VPS26CNM_006052.2 linkc.625G>C p.Val209Leu missense_variant Exon 6 of 8 ENST00000309117.11 NP_006043.1 O14972-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VPS26CENST00000309117.11 linkc.625G>C p.Val209Leu missense_variant Exon 6 of 8 1 NM_006052.2 ENSP00000311399.6 O14972-1

Frequencies

GnomAD3 genomes
AF:
0.000165
AC:
25
AN:
151372
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000730
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:
0.00
Gnomad NFE
AF:
0.000324
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000127
AC:
32
AN:
250998
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135726
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000273
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000350
AC:
512
AN:
1460788
Hom.:
0
Cov.:
31
AF XY:
0.000311
AC XY:
226
AN XY:
726680
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.000447
Gnomad4 OTH exome
AF:
0.000232
GnomAD4 genome
AF:
0.000165
AC:
25
AN:
151372
Hom.:
0
Cov.:
33
AF XY:
0.0000947
AC XY:
7
AN XY:
73922
show subpopulations
Gnomad4 AFR
AF:
0.0000730
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000324
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000855
Hom.:
0
Bravo
AF:
0.000189
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000906
AC:
11
EpiCase
AF:
0.000164
EpiControl
AF:
0.000415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
17
DANN
Benign
0.97
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.42
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.93
D;D;D;D
M_CAP
Benign
0.0077
T
MetaRNN
Benign
0.14
T;T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-1.4
N;N;N;N
REVEL
Benign
0.055
Sift
Benign
0.063
T;T;T;T
Sift4G
Benign
0.10
T;T;T;T
Polyphen
0.26
.;B;.;.
Vest4
0.46
MutPred
0.58
Loss of sheet (P = 0.0457);.;.;.;
MVP
0.18
MPC
0.50
ClinPred
0.10
T
GERP RS
1.3
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs143165732; hg19: chr21-38600557; API