20-2860320-G-A

Position:

• chr20-2860320-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022575.4(VPS16):​c.322G>A​(p.Val108Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VPS16 NM_022575.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16822976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS16	NM_022575.4	c.322G>A	p.Val108Ile	missense_variant	4/24	ENST00000380445.8	NP_072097.2
VPS16	NM_080413.3	c.322G>A	p.Val108Ile	missense_variant	4/20		NP_536338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS16	ENST00000380445.8	c.322G>A	p.Val108Ile	missense_variant	4/24	1	NM_022575.4	ENSP00000369810	P1
VPS16	ENST00000380469.7	c.322G>A	p.Val108Ile	missense_variant	4/20	2		ENSP00000369836
VPS16	ENST00000417508.1	c.16-129G>A		intron_variant		5		ENSP00000409840
VPS16	ENST00000453689.5	c.16-129G>A		intron_variant		3		ENSP00000417031

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Benign	0.82
DEOGEN2	Benign	0.037	T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	0.088
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.43	N;N
MutationTaster	Benign	1.0	D;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.030	N;N
REVEL	Benign	0.044
Sift	Benign	1.0	T;T
Sift4G	Benign	0.79	T;T
Polyphen		0.0050	B;B
Vest4		0.043
MutPred		0.58		Loss of loop (P = 0.2897);Loss of loop (P = 0.2897);
MVP		0.36
MPC		0.19
ClinPred		0.70	D
GERP RS		5.8
Varity_R		0.036
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-2840966;