rs766610118

Variant names:

• chr11-65096261-C-G
• rs766610118
• NM_013265.4:c.11C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-65096261-C-G
• chr11-65096261-C-T

Variant summary

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

The NM_013265.4(VPS51):​c.11C>G​(p.Ala4Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000293 in 1,367,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A4T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: VPS51 NM_013265.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99

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]

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=0.09886363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS51	NM_013265.4	c.11C>G	p.Ala4Gly	missense_variant	Exon 1 of 10	ENST00000279281.8	NP_037397.2
VPS51	NR_073519.2	n.48C>G		non_coding_transcript_exon_variant	Exon 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS51	ENST00000279281.8	c.11C>G	p.Ala4Gly	missense_variant	Exon 1 of 10	1	NM_013265.4	ENSP00000279281.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000293 AC: 4 AN: 1367376 Hom.: 0 Cov.: 32 AF XY: 0.00000444 AC XY: 3 AN XY: 675354

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000660

Gnomad4 NFE exome AF: 9.35e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000540 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.81
DEOGEN2	Benign	0.010	T;T;T;T;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.77	T;T;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.099	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	.;.;N;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.060	N;N;N;N;.
REVEL	Benign	0.070
Sift	Uncertain	0.0090	D;D;D;D;.
Sift4G	Uncertain	0.024	D;T;T;T;.
Polyphen		0.0010	.;.;B;.;.
Vest4		0.27
MutPred		0.29		.;Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);Loss of helix (P = 0.0068);
MVP		0.067
MPC		0.69
ClinPred		0.14	T
GERP RS		-0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.11
gMVP		0.21

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: rs766610118; hg19: chr11-64863733;