20-2840882-C-T

Position:

• chr20-2840882-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.298

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]

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]

ACMG classification

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS16	NM_022575.4	c.53+55C>T		intron_variant		ENST00000380445.8	NP_072097.2
PCED1A	NM_001271168.2	c.-38G>A		5_prime_UTR_variant	1/8		NP_001258097.1
PCED1A	XM_005260804.3	c.-38G>A		5_prime_UTR_variant	1/8		XP_005260861.1
VPS16	NM_080413.3	c.53+55C>T		intron_variant			NP_536338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS16	ENST00000380445.8	c.53+55C>T		intron_variant		1	NM_022575.4	ENSP00000369810	P1

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3545 AN: 151320 Hom.: 81 Cov.: 32

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.: 24 AF XY: 0.0111 AC XY: 7347 AN XY: 663926

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.: 84 Cov.: 32 AF XY: 0.0233 AC XY: 1723 AN XY: 73990

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.: 7

Bravo AF: 0.0254

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 26, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Other links and lift over

dbSNP: rs114441777; hg19: chr20-2821528;