Variant chr20-2860454-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_022575.4(VPS16):c.375G>A(p.Val125=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,614,094 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 6 hom. )

Consequence

VPS16
NM_022575.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0300

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 20-2860454-G-A is Benign according to our data. Variant chr20-2860454-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652157.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.03 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 6 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS16	NM_022575.4 linkuse as main transcript	c.375G>A	p.Val125=	synonymous_variant	5/24	ENST00000380445.8	NP_072097.2
VPS16	NM_080413.3 linkuse as main transcript	c.375G>A	p.Val125=	synonymous_variant	5/20		NP_536338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS16	ENST00000380445.8 linkuse as main transcript	c.375G>A	p.Val125=	synonymous_variant	5/24	1	NM_022575.4	ENSP00000369810	P1	Q9H269-1
VPS16	ENST00000380469.7 linkuse as main transcript	c.375G>A	p.Val125=	synonymous_variant	5/20	2		ENSP00000369836		Q9H269-2
VPS16	ENST00000453689.5 linkuse as main transcript	c.21G>A	p.Val7=	synonymous_variant	3/10	3		ENSP00000417031
VPS16	ENST00000417508.1 linkuse as main transcript	c.21G>A	p.Val7=	synonymous_variant	3/9	5		ENSP00000409840

Frequencies

GnomAD3 genomes

AF:

0.00139

AC:

211

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00234

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00134

AC:

338

AN:

251444

Hom.:

AF XY:

0.00133

AC XY:

181

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00105

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00209

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00172

AC:

2518

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00170

AC XY:

1239

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00110

Gnomad4 FIN exome

AF:

0.00198

Gnomad4 NFE exome

AF:

0.00196

Gnomad4 OTH exome

AF:

0.00179

GnomAD4 genome

AF:

0.00139

AC:

211

AN:

152232

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

106

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00234

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00206

Hom.:

Bravo

AF:

0.00119

EpiCase

AF:

0.00191

EpiControl

AF:

0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

VPS16: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.23

DANN

Benign

0.74

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