20-2845326-G-C

Position:

• chr20-2845326-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_022575.4(VPS16):​c.53+4499G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000381 in 152,078 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00038 (1 hom., cov: 31)
• Consequence: VPS16 NM_022575.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000381 (58/152078) while in subpopulation EAS AF= 0.00658 (34/5170). AF 95% confidence interval is 0.00484. There are 1 homozygotes in gnomad4. There are 31 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS16	NM_022575.4	c.53+4499G>C		intron_variant		ENST00000380445.8	NP_072097.2
VPS16	NM_080413.3	c.53+4499G>C		intron_variant			NP_536338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS16	ENST00000380445.8	c.53+4499G>C		intron_variant		1	NM_022575.4	ENSP00000369810.3
VPS16	ENST00000380469.7	c.53+4499G>C		intron_variant		2		ENSP00000369836.3
VPS16	ENST00000453689.5	c.-75+4499G>C		intron_variant		3		ENSP00000417031.1
VPS16	ENST00000417508.1	c.-75+4499G>C		intron_variant		5		ENSP00000409840.1

Frequencies

GnomAD3 genomes AF: 0.000395 AC: 60 AN: 151960 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00656

Gnomad SAS AF: 0.00540

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000381 AC: 58 AN: 152078 Hom.: 1 Cov.: 31 AF XY: 0.000417 AC XY: 31 AN XY: 74322

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00658

Gnomad4 SAS AF: 0.00499

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.7
DANN	Benign	0.56

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: rs6132977; hg19: chr20-2825972;