16-70741552-C-T

Variant names:

• chr16-70741552-C-T
• rs875858
• NM_018052.5:c.1528+2871G>A

Variant summary

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

The NM_018052.5(VAC14):​c.1528+2871G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 152,272 control chromosomes in the GnomAD database, including 299 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 0.049 (299 hom., cov: 33)
• Consequence: VAC14 NM_018052.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.935
• Publications: 14 publications found

Genes affected

VAC14 (HGNC:25507): (VAC14 component of PIKFYVE complex) This gene encodes a scaffold protein that is a component of the PIKfyve protein kinase complex. This complex is responsible for the synthesis of phosphatidylinositol 3,5-bisphosphate, an important component of cellular membranes, from phosphatidylinositol 3-phosphate. Mice lacking a functional copy of this gene exhibit severe neurodegeneration. Mutations in the human gene have been identified in patients with a childhood onset progressive neurological disorder characterized by impaired movement, dystonia, and striatal abnormalities. [provided by RefSeq, May 2017]

VAC14 Gene-Disease associations (from GenCC):

• striatonigral degeneration, childhood-onset

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hereditary neurological disease

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• Yunis-Varon syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000260156 (HGNC:58481):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018052.5. 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
	VAC14	NM_018052.5	MANE Select	c.1528+2871G>A		intron	N/A	NP_060522.3
	VAC14	NM_001351157.2		c.826+2871G>A		intron	N/A	NP_001338086.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAC14	ENST00000261776.10	TSL:1 MANE Select	c.1528+2871G>A		intron	N/A	ENSP00000261776.5
	VAC14	ENST00000564685.5	TSL:1	n.216+2871G>A		intron	N/A
	VAC14	ENST00000568548.5	TSL:1	n.*1254+2871G>A		intron	N/A	ENSP00000454650.1

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7461 AN: 152154 Hom.: 299 Cov.: 33

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0421

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0375

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0618

Gnomad OTH AF: 0.0522

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

GnomAD4 genome AF: 0.0490 AC: 7462 AN: 152272 Hom.: 299 Cov.: 33 AF XY: 0.0528 AC XY: 3930 AN XY: 74448

African (AFR) AF: 0.0113 AC: 468 AN: 41560

American (AMR) AF: 0.0421 AC: 644 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 225 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0373 AC: 180 AN: 4826

European-Finnish (FIN) AF: 0.146 AC: 1550 AN: 10604

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0618 AC: 4205 AN: 68014

Other (OTH) AF: 0.0511 AC: 108 AN: 2112

Alfa AF: 0.0516 Hom.: 273

Bravo AF: 0.0392

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.30
DANN	Benign	0.75
PhyloP100		-0.94
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: rs875858; hg19: chr16-70775455;