NM_022575.4:c.53+4499G>A

Variant names:

• chr20-2845326-G-A
• rs6132977
• NM_022575.4:c.53+4499G>A

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+4499G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0683 in 152,050 control chromosomes in the GnomAD database, including 677 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 (677 hom., cov: 31)
• Consequence: VPS16 NM_022575.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS16	NM_022575.4	c.53+4499G>A		intron_variant	Intron 1 of 23	ENST00000380445.8	NP_072097.2
VPS16	NM_080413.3	c.53+4499G>A		intron_variant	Intron 1 of 19		NP_536338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS16	ENST00000380445.8	c.53+4499G>A		intron_variant	Intron 1 of 23	1	NM_022575.4	ENSP00000369810.3
VPS16	ENST00000380469.7	c.53+4499G>A		intron_variant	Intron 1 of 19	2		ENSP00000369836.3
VPS16	ENST00000453689.5	c.-75+4499G>A		intron_variant	Intron 1 of 9	3		ENSP00000417031.1
VPS16	ENST00000417508.1	c.-75+4499G>A		intron_variant	Intron 1 of 8	5		ENSP00000409840.1

Frequencies

GnomAD3 genomes AF: 0.0680 AC: 10334 AN: 151932 Hom.: 662 Cov.: 31

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.0875

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.0217

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0121

Gnomad OTH AF: 0.0647

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

GnomAD4 genome AF: 0.0683 AC: 10379 AN: 152050 Hom.: 677 Cov.: 31 AF XY: 0.0703 AC XY: 5225 AN XY: 74308

African (AFR) AF: 0.147 AC: 6103 AN: 41454

American (AMR) AF: 0.135 AC: 2067 AN: 15260

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

East Asian (EAS) AF: 0.0871 AC: 450 AN: 5168

South Asian (SAS) AF: 0.0939 AC: 452 AN: 4812

European-Finnish (FIN) AF: 0.0217 AC: 230 AN: 10576

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

European-Non Finnish (NFE) AF: 0.0121 AC: 824 AN: 67994

Other (OTH) AF: 0.0640 AC: 135 AN: 2108

Alfa AF: 0.0373 Hom.: 459

Bravo AF: 0.0815

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.54
PhyloP100		-0.070
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: rs6132977; hg19: chr20-2825972;