7-93256521-G-A

Variant names:

• chr7-93256521-G-A
• NM_017667.4:c.310G>A

Variant summary

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

The NM_017667.4(VPS50):​c.310G>A​(p.Val104Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VPS50 NM_017667.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.93

Genes affected

VPS50 (HGNC:25956): (VPS50 subunit of EARP/GARPII complex) Enables SNARE binding activity. Acts upstream of or within endocytic recycling. Located in recycling endosome. Part of EARP complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS50	NM_017667.4	c.310G>A	p.Val104Met	missense_variant	Exon 5 of 28	ENST00000305866.10	NP_060137.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS50	ENST00000305866.10	c.310G>A	p.Val104Met	missense_variant	Exon 5 of 28	1	NM_017667.4	ENSP00000307666.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1284118 Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0 AN XY: 641840

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.310G>A (p.V104M) alteration is located in exon 5 (coding exon 5) of the VPS50 gene. This alteration results from a G to A substitution at nucleotide position 310, causing the valine (V) at amino acid position 104 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	0.71
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	.;T;.;T
Eigen	Pathogenic	0.68
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	D;D;D;D
M_CAP	Benign	0.0092	T
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Benign	-0.47	T
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.7	N;N;N;N
REVEL	Benign	0.26
Sift	Benign	0.052	T;T;T;D
Sift4G	Uncertain	0.041	D;T;T;D
Polyphen		0.94	P;D;.;.
Vest4		0.86
MutPred		0.46		Gain of catalytic residue at V100 (P = 0.0205);Gain of catalytic residue at V100 (P = 0.0205);.;.;
MVP		0.63
MPC		1.2
ClinPred		0.83	D
GERP RS		5.5
Varity_R		0.25
gMVP		0.48

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-92885833;