Variant 20-2840882-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_022575.4(VPS16):c.53+55C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,496,706 control chromosomes in the GnomAD database, including 255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.024 ( 84 hom., cov: 32)

Exomes 𝑓: 0.010 ( 171 hom. )

Consequence

VPS16
NM_022575.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.298

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:

PCED1A (HGNC:16212): (PC-esterase domain containing 1A) The protein encoded by this gene is a member of the GDSL/SGNH superfamily. Members of this family are hydrolytic enzymes with esterase and lipase activity and broad substrate specificity. This protein belongs to the Pmr5-Cas1p-esterase subfamily in that it contains the catalytic triad comprised of serine, aspartate and histidine and lacks two conserved regions (glycine after strand S2 and GxND motif). A pseudogene of this gene has been identified on the long arm of chromosome 2. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Sep 2012]

PCED1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 20-2840882-C-T is Benign according to our data. Variant chr20-2840882-C-T is described in ClinVar as [Benign]. Clinvar id is 1259313.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
VPS16	NM_022575.4 linkuse as main transcript	c.53+55C>T	intron_variant		ENST00000380445.8
PCED1A	NM_001271168.2 linkuse as main transcript	c.-38G>A	5_prime_UTR_variant	1/8
PCED1A	XM_005260804.3 linkuse as main transcript	c.-38G>A	5_prime_UTR_variant	1/8
VPS16	NM_080413.3 linkuse as main transcript	c.53+55C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS16	ENST00000380445.8 linkuse as main transcript	c.53+55C>T		intron_variant		1	NM_022575.4	P1	Q9H269-1

Frequencies

GnomAD3 genomes

AF:

0.0234

AC:

3545

AN:

151320

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0575

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0150

Gnomad ASJ

AF:

0.0260

Gnomad EAS

AF:

0.000977

Gnomad SAS

AF:

0.0328

Gnomad FIN

AF:

0.00585

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00848

Gnomad OTH

AF:

0.0212

GnomAD4 exome

AF:

0.0105

AC:

14110

AN:

1345266

Hom.:

171

Cov.:

AF XY:

0.0111

AC XY:

7347

AN XY:

663926

show subpopulations

Gnomad4 AFR exome

AF:

0.0584

Gnomad4 AMR exome

AF:

0.00835

Gnomad4 ASJ exome

AF:

0.0260

Gnomad4 EAS exome

AF:

0.000914

Gnomad4 SAS exome

AF:

0.0306

Gnomad4 FIN exome

AF:

0.00859

Gnomad4 NFE exome

AF:

0.00750

Gnomad4 OTH exome

AF:

0.0146

GnomAD4 genome

AF:

0.0235

AC:

3559

AN:

151440

Hom.:

Cov.:

AF XY:

0.0233

AC XY:

1723

AN XY:

73990

show subpopulations

Gnomad4 AFR

AF:

0.0578

Gnomad4 AMR

AF:

0.0150

Gnomad4 ASJ

AF:

0.0260

Gnomad4 EAS

AF:

0.000979

Gnomad4 SAS

AF:

0.0320

Gnomad4 FIN

AF:

0.00585

Gnomad4 NFE

AF:

0.00848

Gnomad4 OTH

AF:

0.0205

Alfa

AF:

0.0203

Hom.:

Bravo

AF:

0.0254

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 26, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.4

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