rs2297048

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_022575.4(VPS16):c.285G>A(p.Glu95Glu) 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

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

dystonia 30
Inheritance: AR, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
isolated dystonia
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

VPS16 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
VPS16	NM_022575.4 link	c.285G>A	p.Glu95Glu	synonymous_variant	Exon 4 of 24	ENST00000380445.8	NP_072097.2	Q9H269-1
VPS16	NM_080413.3 link	c.285G>A	p.Glu95Glu	synonymous_variant	Exon 4 of 20		NP_536338.1	Q9H269-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
VPS16	ENST00000380445.8 link	c.285G>A	p.Glu95Glu	synonymous_variant	Exon 4 of 24	1	NM_022575.4	ENSP00000369810.3	Q9H269-1
VPS16	ENST00000380469.7 link	c.285G>A	p.Glu95Glu	synonymous_variant	Exon 4 of 20	2		ENSP00000369836.3	Q9H269-2
VPS16	ENST00000453689.5 link	c.16-166G>A		intron_variant	Intron 2 of 9	3		ENSP00000417031.1	Q5JUA9
VPS16	ENST00000417508.1 link	c.16-166G>A		intron_variant	Intron 2 of 8	5		ENSP00000409840.1	Q5JUB0

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

GnomAD2 exomes

AF:

0.0315

AC:

7912

AN:

251390

AF XY:

0.0260

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 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

African (AFR)

AF:

0.00158

AC:

AN:

33480

American (AMR)

AF:

0.146

AC:

6544

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000765

AC:

AN:

26136

East Asian (EAS)

AF:

0.0721

AC:

2862

AN:

39700

South Asian (SAS)

AF:

0.0127

AC:

1093

AN:

86256

European-Finnish (FIN)

AF:

0.0116

AC:

619

AN:

53412

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00252

AC:

2803

AN:

1112008

Other (OTH)

AF:

0.0111

AC:

672

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

977

1953

2930

3906

4883

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

244

488

732

976

1220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0155

AC:

2364

AN:

152234

Hom.:

123

Cov.:

AF XY:

0.0176

AC XY:

1313

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.00248

AC:

103

AN:

41540

American (AMR)

AF:

0.0897

AC:

1371

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.0851

AC:

439

AN:

5158

South Asian (SAS)

AF:

0.0141

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0161

AC:

171

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00235

AC:

160

AN:

68014

Other (OTH)

AF:

0.0227

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

105

210

315

420

525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0108

Hom.:

136

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

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

8.6

(source)

DANN

Benign

0.78

PhyloP100

0.96

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over