chr11-65096319-G-C

Position:

• chr11-65096319-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013265.4(VPS51):​c.69G>C​(p.Glu23Asp) 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 benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VPS51 NM_013265.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.699

Genes affected

VPS51 (HGNC:1172): (VPS51 subunit of GARP complex) This gene encodes a member of the vacuolar protein sorting-associated protein 51 family. The encoded protein is a component of the Golgi-associated retrograde protein complex which acts as a tethering factor for carriers in retrograde transport from the early and late endosomes to the trans-Golgi network. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

VPS51 (HGNC:):

ACMG classification

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=0.08055624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS51	NM_013265.4	c.69G>C	p.Glu23Asp	missense_variant	1/10	ENST00000279281.8	NP_037397.2
VPS51	NR_073519.2	n.106G>C		non_coding_transcript_exon_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS51	ENST00000279281.8	c.69G>C	p.Glu23Asp	missense_variant	1/10	1	NM_013265.4	ENSP00000279281.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.69G>C (p.E23D) alteration is located in exon 1 (coding exon 1) of the VPS51 gene. This alteration results from a G to C substitution at nucleotide position 69, causing the glutamic acid (E) at amino acid position 23 to be replaced by an aspartic acid (D). 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	0.086
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.2
DANN	Benign	0.94
DEOGEN2	Benign	0.0028	T;T;T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.61	T;T;T;T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.081	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	.;.;L;.;.
MutationTaster	Benign	1.0	N
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	0.10	N;N;N;N;.
REVEL	Benign	0.11
Sift	Benign	0.18	T;T;T;T;.
Sift4G	Benign	0.37	T;T;T;T;.
Polyphen		0.033	.;.;B;.;.
Vest4		0.087
MutPred		0.13		.;Loss of glycosylation at P27 (P = 0.1314);Loss of glycosylation at P27 (P = 0.1314);Loss of glycosylation at P27 (P = 0.1314);Loss of glycosylation at P27 (P = 0.1314);
MVP		0.085
MPC		0.63
ClinPred		0.14	T
GERP RS		-2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.054
gMVP		0.10

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: chr11-64863791;