rs7185187

Variant names:

• chr16-70723652-C-T
• rs7185187
• NM_018052.5:c.1661+7843G>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.1661+7843G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,220 control chromosomes in the GnomAD database, including 7,261 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 0.22 (7261 hom., cov: 33)
• Consequence: VAC14 NM_018052.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251
• Publications: 10 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAC14	NM_018052.5	c.1661+7843G>A		intron_variant	Intron 14 of 18	ENST00000261776.10	NP_060522.3
VAC14	NM_001351157.2	c.959+7843G>A		intron_variant	Intron 13 of 17		NP_001338086.1
VAC14	XM_005256038.5	c.1661+7843G>A		intron_variant	Intron 14 of 18		XP_005256095.1
VAC14	XM_011523225.4	c.1662-2809G>A		intron_variant	Intron 14 of 14		XP_011521527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAC14	ENST00000261776.10	c.1661+7843G>A		intron_variant	Intron 14 of 18	1	NM_018052.5	ENSP00000261776.5

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32959 AN: 152102 Hom.: 7223 Cov.: 33

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0728

Gnomad SAS AF: 0.0715

Gnomad FIN AF: 0.0244

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.0820

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.217 AC: 33050 AN: 152220 Hom.: 7261 Cov.: 33 AF XY: 0.209 AC XY: 15577 AN XY: 74428

African (AFR) AF: 0.569 AC: 23598 AN: 41478

American (AMR) AF: 0.130 AC: 1985 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3472

East Asian (EAS) AF: 0.0730 AC: 379 AN: 5194

South Asian (SAS) AF: 0.0703 AC: 339 AN: 4822

European-Finnish (FIN) AF: 0.0244 AC: 259 AN: 10620

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.0820 AC: 5580 AN: 68014

Other (OTH) AF: 0.197 AC: 416 AN: 2114

Alfa AF: 0.127 Hom.: 4770

Bravo AF: 0.240

Asia WGS AF: 0.127 AC: 444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.54
PhyloP100		0.25
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: rs7185187; hg19: chr16-70757555;