Variant 11-134225276-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_052875.5(VPS26B):c.154C>G(p.Leu52Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,836 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: 6.8e-7 ( 0 hom. )

Consequence

VPS26B
NM_052875.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42

Variant links:

Genes affected

VPS26B (HGNC:28119): (VPS26 retromer complex component B) Predicted to be involved in intracellular protein transport and retrograde transport, endosome to Golgi. Predicted to act upstream of or within cellular response to interferon-gamma. Predicted to be located in early endosome and late endosome. Predicted to be part of retromer complex. Predicted to be active in endosome. [provided by Alliance of Genome Resources, Apr 2022]

VPS26B links:

NCAPD3 (HGNC:28952): (non-SMC condensin II complex subunit D3) Condensin complexes I and II play essential roles in mitotic chromosome assembly and segregation. Both condensins contain 2 invariant structural maintenance of chromosome (SMC) subunits, SMC2 (MIM 605576) and SMC4 (MIM 605575), but they contain different sets of non-SMC subunits. NCAPD3 is 1 of 3 non-SMC subunits that define condensin II (Ono et al., 2003 [PubMed 14532007]).[supplied by OMIM, Mar 2008]

NCAPD3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05725524).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VPS26B	NM_052875.5 linkuse as main transcript	c.154C>G	p.Leu52Val	missense_variant	1/6	ENST00000281187.10	NP_443107.1
VPS26B	XM_011542565.4 linkuse as main transcript	c.154C>G	p.Leu52Val	missense_variant	1/4		XP_011540867.1
NCAPD3	NM_001372070.1 linkuse as main transcript	c.-769G>C		5_prime_UTR_variant	1/37		NP_001358999.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS26B	ENST00000281187.10 linkuse as main transcript	c.154C>G	p.Leu52Val	missense_variant	1/6	1	NM_052875.5	ENSP00000281187	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jul 14, 2021

The c.154C>G (p.L52V) alteration is located in exon 1 (coding exon 1) of the VPS26B gene. This alteration results from a C to G substitution at nucleotide position 154, causing the leucine (L) at amino acid position 52 to be replaced by a valine (V). 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

0.053

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.028

T;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.89

.;D

M_CAP

Benign

0.0085

MetaRNN

Benign

0.057

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.55

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

1.7

N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T

Sift4G

Benign

0.86

T;T

Polyphen

0.0

B;B

Vest4

0.18

MutPred

0.45

Gain of methylation at K55 (P = 0.1254);Gain of methylation at K55 (P = 0.1254);

MVP

0.068

MPC

0.91

ClinPred

0.62

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.059

gMVP

0.38

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