11-134245469-A-G

Variant names:

• chr11-134245469-A-G
• rs1427612035
• NM_052875.5:c.890A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_052875.5(VPS26B):​c.890A>G​(p.Asp297Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: VPS26B NM_052875.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.01
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40978822).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052875.5. 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
	VPS26B	NM_052875.5	MANE Select	c.890A>G	p.Asp297Gly	missense	Exon 6 of 6	NP_443107.1	Q4G0F5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS26B	ENST00000281187.10	TSL:1 MANE Select	c.890A>G	p.Asp297Gly	missense	Exon 6 of 6	ENSP00000281187.5	Q4G0F5
	VPS26B	ENST00000911843.1		c.959A>G	p.Asp320Gly	missense	Exon 6 of 6	ENSP00000581902.1
	VPS26B	ENST00000957932.1		c.905A>G	p.Asp302Gly	missense	Exon 6 of 6	ENSP00000627991.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		7.0
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.022	D
Polyphen		0.65	P
Vest4		0.56
MutPred		0.41		Loss of helix (P = 0.0558)
MVP		0.35
MPC		1.5
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.55
gMVP		0.96
Mutation Taster		=16/84	disease causing

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

Other links and lift over

dbSNP: rs1427612035; hg19: chr11-134115363;