20-2860283-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_022575.4(VPS16):c.285G>A(p.Glu95=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,614,112 control chromosomes in the GnomAD database, including 828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (123 hom., cov: 32)
  • Exomes 𝑓: 0.010 (705 hom.)
• Consequence: VPS16 NM_022575.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.962

Genes affected

VPS16 (HGNC:14584): (VPS16 core subunit of CORVET and HOPS complexes) Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene encodes the human homolog of yeast class C Vps16 protein. The mammalian class C Vps proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2009]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 20-2860283-G-A is Benign according to our data. Variant chr20-2860283-G-A is described in ClinVar as [Benign]. Clinvar id is 1272504.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.962 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS16	NM_022575.4	c.285G>A	p.Glu95=	synonymous_variant	4/24	ENST00000380445.8
VPS16	NM_080413.3	c.285G>A	p.Glu95=	synonymous_variant	4/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS16	ENST00000380445.8	c.285G>A	p.Glu95=	synonymous_variant	4/24	1	NM_022575.4	P1
VPS16	ENST00000380469.7	c.285G>A	p.Glu95=	synonymous_variant	4/20	2
VPS16	ENST00000417508.1	c.16-166G>A		intron_variant		5
VPS16	ENST00000453689.5	c.16-166G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2350 AN: 152116 Hom.: 116 Cov.: 32

Gnomad AFR AF: 0.00249

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0885

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0855

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00235

Gnomad OTH AF: 0.0225

GnomAD3 exomes AF: 0.0315 AC: 7912 AN: 251390 Hom.: 515 AF XY: 0.0260 AC XY: 3537 AN XY: 135878

Gnomad AFR exome AF: 0.00265

Gnomad AMR exome AF: 0.150

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.0827

Gnomad SAS exome AF: 0.0135

Gnomad FIN exome AF: 0.0138

Gnomad NFE exome AF: 0.00254

Gnomad OTH exome AF: 0.0251

GnomAD4 exome AF: 0.0100 AC: 14677 AN: 1461878 Hom.: 705 Cov.: 33 AF XY: 0.00951 AC XY: 6918 AN XY: 727238

Gnomad4 AFR exome AF: 0.00158

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.000765

Gnomad4 EAS exome AF: 0.0721

Gnomad4 SAS exome AF: 0.0127

Gnomad4 FIN exome AF: 0.0116

Gnomad4 NFE exome AF: 0.00252

Gnomad4 OTH exome AF: 0.0111

GnomAD4 genome AF: 0.0155 AC: 2364 AN: 152234 Hom.: 123 Cov.: 32 AF XY: 0.0176 AC XY: 1313 AN XY: 74420

Gnomad4 AFR AF: 0.00248

Gnomad4 AMR AF: 0.0897

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0851

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.0161

Gnomad4 NFE AF: 0.00235

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00923 Hom.: 95

Bravo AF: 0.0221

Asia WGS AF: 0.0590 AC: 203 AN: 3478

EpiCase AF: 0.00234

EpiControl AF: 0.00225

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	8.6
Dann	Benign	0.78

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: rs2297048; hg19: chr20-2840929; COSMIC: COSV66795382; COSMIC: COSV66795382;