Variant rs2297048 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.962

Variant links:

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]

VPS16 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
VPS16	NM_022575.4 linkuse as main transcript	c.285G>A	p.Glu95=	synonymous_variant	4/24	ENST00000380445.8	NP_072097.2
VPS16	NM_080413.3 linkuse as main transcript	c.285G>A	p.Glu95=	synonymous_variant	4/20		NP_536338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS16	ENST00000380445.8 linkuse as main transcript	c.285G>A	p.Glu95=	synonymous_variant	4/24	1	NM_022575.4	ENSP00000369810	P1	Q9H269-1
VPS16	ENST00000380469.7 linkuse as main transcript	c.285G>A	p.Glu95=	synonymous_variant	4/20	2		ENSP00000369836		Q9H269-2
VPS16	ENST00000417508.1 linkuse as main transcript	c.16-166G>A		intron_variant		5		ENSP00000409840
VPS16	ENST00000453689.5 linkuse as main transcript	c.16-166G>A		intron_variant		3		ENSP00000417031

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2350

AN:

152116

Hom.:

116

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.00951

AC XY:

6918

AN XY:

727238

show subpopulations

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.:

AF XY:

0.0176

AC XY:

1313

AN XY:

74420

show subpopulations

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.:

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over