NM_022575.4:c.53+4848A>G

Variant names:

• chr20-2845675-A-G
• rs6132978
• NM_022575.4:c.53+4848A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022575.4(VPS16):​c.53+4848A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0676 in 152,046 control chromosomes in the GnomAD database, including 673 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 0.068 (673 hom., cov: 31)
• Consequence: VPS16 NM_022575.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022575.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS16	NM_022575.4	MANE Select	c.53+4848A>G		intron	N/A	NP_072097.2
	VPS16	NM_080413.3		c.53+4848A>G		intron	N/A	NP_536338.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS16	ENST00000380445.8	TSL:1 MANE Select	c.53+4848A>G		intron	N/A	ENSP00000369810.3
	VPS16	ENST00000967591.1		c.53+4848A>G		intron	N/A	ENSP00000637650.1
	VPS16	ENST00000876979.1		c.53+4848A>G		intron	N/A	ENSP00000547038.1

Frequencies

GnomAD3 genomes AF: 0.0674 AC: 10236 AN: 151928 Hom.: 658 Cov.: 31

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.0881

Gnomad SAS AF: 0.0779

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.0641

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

GnomAD4 genome AF: 0.0676 AC: 10282 AN: 152046 Hom.: 673 Cov.: 31 AF XY: 0.0694 AC XY: 5156 AN XY: 74318

African (AFR) AF: 0.147 AC: 6091 AN: 41428

American (AMR) AF: 0.136 AC: 2068 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 100 AN: 3472

East Asian (EAS) AF: 0.0877 AC: 454 AN: 5176

South Asian (SAS) AF: 0.0761 AC: 366 AN: 4810

European-Finnish (FIN) AF: 0.0219 AC: 232 AN: 10590

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0120 AC: 819 AN: 68002

Other (OTH) AF: 0.0634 AC: 134 AN: 2114

Alfa AF: 0.0462 Hom.: 50

Bravo AF: 0.0814

Asia WGS AF: 0.0970 AC: 336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.1
DANN	Benign	0.76
PhyloP100		0.055
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6132978; hg19: chr20-2826321;