11-134243173-C-G

Variant names:

• chr11-134243173-C-G
• NM_052875.5:c.600C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_052875.5(VPS26B):​c.600C>G​(p.Ile200Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: VPS26B NM_052875.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.99

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.854

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS26B	NM_052875.5	c.600C>G	p.Ile200Met	missense_variant	Exon 4 of 6	ENST00000281187.10	NP_443107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS26B	ENST00000281187.10	c.600C>G	p.Ile200Met	missense_variant	Exon 4 of 6	1	NM_052875.5	ENSP00000281187.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.600C>G (p.I200M) alteration is located in exon 4 (coding exon 4) of the VPS26B gene. This alteration results from a C to G substitution at nucleotide position 600, causing the isoleucine (I) at amino acid position 200 to be replaced by a methionine (M). 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	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T;T
Eigen	Pathogenic	0.72
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	.;D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Uncertain	0.10	D
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.8	D;.
REVEL	Uncertain	0.45
Sift	Uncertain	0.0010	D;.
Sift4G	Benign	0.072	T;T
Polyphen		0.99	D;D
Vest4		0.85
MutPred		0.71		Loss of stability (P = 0.0812);Loss of stability (P = 0.0812);
MVP		0.40
MPC		1.6
ClinPred		0.94	D
GERP RS		4.9
Varity_R		0.73
gMVP		0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-134113067;