NM_052875.5:c.837G>A

Variant names:

• chr11-134245053-G-A
• rs1555057911
• NM_052875.5:c.837G>A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_052875.5(VPS26B):​c.837G>A​(p.Glu279Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=1.78 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS26B	NM_052875.5	c.837G>A	p.Glu279Glu	synonymous_variant	Exon 5 of 6	ENST00000281187.10	NP_443107.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS26B	ENST00000281187.10	c.837G>A	p.Glu279Glu	synonymous_variant	Exon 5 of 6	1	NM_052875.5	ENSP00000281187.5
VPS26B	ENST00000525095.2	c.837G>A	p.Glu279Glu	synonymous_variant	Exon 6 of 7	5		ENSP00000434162.2
VPS26B	ENST00000531741.1	n.1202G>A		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.3
DANN	Benign	0.88

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

Other links and lift over

dbSNP: rs1555057911; hg19: chr11-134114947;