Variant 16-70762632-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000261776.10(VAC14):c.1306-27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 1,609,798 control chromosomes in the GnomAD database, including 320,071 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27824 hom., cov: 33)

Exomes 𝑓: 0.63 ( 292247 hom. )

Consequence

VAC14
ENST00000261776.10 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.59

Variant links:

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 links:

VAC14-AS1 (HGNC:):

VAC14-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 16-70762632-C-T is Benign according to our data. Variant chr16-70762632-C-T is described in ClinVar as [Benign]. Clinvar id is 1183222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VAC14	NM_018052.5 linkuse as main transcript	c.1306-27G>A		intron_variant		ENST00000261776.10	NP_060522.3	Q08AM6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VAC14	ENST00000261776.10 linkuse as main transcript	c.1306-27G>A		intron_variant		1	NM_018052.5	ENSP00000261776.5		Q08AM6-1

Frequencies

GnomAD3 genomes

AF:

0.600

AC:

90991

AN:

151566

Hom.:

27812

Cov.:

show subpopulations

Gnomad AFR

AF:

0.479

Gnomad AMI

AF:

0.588

Gnomad AMR

AF:

0.719

Gnomad ASJ

AF:

0.651

Gnomad EAS

AF:

0.525

Gnomad SAS

AF:

0.648

Gnomad FIN

AF:

0.696

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.632

Gnomad OTH

AF:

0.622

GnomAD3 exomes

AF:

0.647

AC:

160106

AN:

247514

Hom.:

52450

AF XY:

0.645

AC XY:

86310

AN XY:

133782

show subpopulations

Gnomad AFR exome

AF:

0.480

Gnomad AMR exome

AF:

0.797

Gnomad ASJ exome

AF:

0.653

Gnomad EAS exome

AF:

0.524

Gnomad SAS exome

AF:

0.649

Gnomad FIN exome

AF:

0.698

Gnomad NFE exome

AF:

0.634

Gnomad OTH exome

AF:

0.655

GnomAD4 exome

AF:

0.631

AC:

919662

AN:

1458114

Hom.:

292247

Cov.:

AF XY:

0.632

AC XY:

458063

AN XY:

725298

show subpopulations

Gnomad4 AFR exome

AF:

0.472

Gnomad4 AMR exome

AF:

0.792

Gnomad4 ASJ exome

AF:

0.653

Gnomad4 EAS exome

AF:

0.560

Gnomad4 SAS exome

AF:

0.652

Gnomad4 FIN exome

AF:

0.695

Gnomad4 NFE exome

AF:

0.627

Gnomad4 OTH exome

AF:

0.620

GnomAD4 genome

AF:

0.600

AC:

91030

AN:

151684

Hom.:

27824

Cov.:

AF XY:

0.606

AC XY:

44873

AN XY:

74086

show subpopulations

Gnomad4 AFR

AF:

0.479

Gnomad4 AMR

AF:

0.720

Gnomad4 ASJ

AF:

0.651

Gnomad4 EAS

AF:

0.524

Gnomad4 SAS

AF:

0.648

Gnomad4 FIN

AF:

0.696

Gnomad4 NFE

AF:

0.632

Gnomad4 OTH

AF:

0.624

Alfa

AF:

0.628

Hom.:

5613

Bravo

AF:

0.600

Asia WGS

AF:

0.572

AC:

1992

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Striatonigral degeneration, childhood-onset

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.0030

DANN

Benign

0.69

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over