rs145401972

Variant names:

• chr16-70687980-C-A
• rs145401972
• NM_018052.5:c.2297G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-70687980-C-A
• chr16-70687980-C-T

Variant summary

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

The NM_018052.5(VAC14):​c.2297G>T​(p.Arg766Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R766Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: VAC14 NM_018052.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.83

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAC14	NM_018052.5	c.2297G>T	p.Arg766Leu	missense_variant	Exon 19 of 19	ENST00000261776.10	NP_060522.3
VAC14	NM_001351157.2	c.1595G>T	p.Arg532Leu	missense_variant	Exon 18 of 18		NP_001338086.1
VAC14	XM_005256038.5	c.*3883G>T		3_prime_UTR_variant	Exon 19 of 19		XP_005256095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAC14	ENST00000261776.10	c.2297G>T	p.Arg766Leu	missense_variant	Exon 19 of 19	1	NM_018052.5	ENSP00000261776.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.50	D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.0	L;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.4	N;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0020	D;D
Sift4G	Benign	0.13	T;D
Polyphen		0.99	D;.
Vest4		0.56
MutPred		0.55		Loss of MoRF binding (P = 0.0173);.;
MVP		0.38
MPC		0.62
ClinPred		0.95	D
GERP RS		4.5
Varity_R		0.54
gMVP		0.53

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

LitVar

Other links and lift over

dbSNP: rs145401972; hg19: chr16-70721883;