Variant 16-70762612-G-A 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 NM_018052.5(VAC14):c.1306-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,611,754 control chromosomes in the GnomAD database, including 332,612 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 28824 hom., cov: 33)

Exomes 𝑓: 0.64 ( 303788 hom. )

Consequence

VAC14
NM_018052.5 splice_region, intron

Scores

Splicing: ADA: 0.00001623

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.31

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 16-70762612-G-A is Benign according to our data. Variant chr16-70762612-G-A is described in ClinVar as [Benign]. Clinvar id is 1269382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.716 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.1306-7C>T		splice_region_variant, 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.1306-7C>T		splice_region_variant, intron_variant		1	NM_018052.5	ENSP00000261776.5		Q08AM6-1

Frequencies

GnomAD3 genomes

AF:

0.612

AC:

92716

AN:

151514

Hom.:

28814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.496

Gnomad AMI

AF:

0.589

Gnomad AMR

AF:

0.727

Gnomad ASJ

AF:

0.661

Gnomad EAS

AF:

0.532

Gnomad SAS

AF:

0.650

Gnomad FIN

AF:

0.697

Gnomad MID

AF:

0.652

Gnomad NFE

AF:

0.644

Gnomad OTH

AF:

0.638

GnomAD3 exomes

AF:

0.656

AC:

163540

AN:

249122

Hom.:

54440

AF XY:

0.655

AC XY:

88177

AN XY:

134670

show subpopulations

Gnomad AFR exome

AF:

0.498

Gnomad AMR exome

AF:

0.804

Gnomad ASJ exome

AF:

0.662

Gnomad EAS exome

AF:

0.532

Gnomad SAS exome

AF:

0.653

Gnomad FIN exome

AF:

0.699

Gnomad NFE exome

AF:

0.646

Gnomad OTH exome

AF:

0.665

GnomAD4 exome

AF:

0.643

AC:

938673

AN:

1460122

Hom.:

303788

Cov.:

AF XY:

0.644

AC XY:

467436

AN XY:

726358

show subpopulations

Gnomad4 AFR exome

AF:

0.487

Gnomad4 AMR exome

AF:

0.799

Gnomad4 ASJ exome

AF:

0.662

Gnomad4 EAS exome

AF:

0.568

Gnomad4 SAS exome

AF:

0.656

Gnomad4 FIN exome

AF:

0.697

Gnomad4 NFE exome

AF:

0.641

Gnomad4 OTH exome

AF:

0.631

GnomAD4 genome

AF:

0.612

AC:

92752

AN:

151632

Hom.:

28824

Cov.:

AF XY:

0.616

AC XY:

45657

AN XY:

74074

show subpopulations

Gnomad4 AFR

AF:

0.495

Gnomad4 AMR

AF:

0.728

Gnomad4 ASJ

AF:

0.661

Gnomad4 EAS

AF:

0.532

Gnomad4 SAS

AF:

0.651

Gnomad4 FIN

AF:

0.697

Gnomad4 NFE

AF:

0.644

Gnomad4 OTH

AF:

0.639

Alfa

AF:

0.644

Hom.:

47074

Bravo

AF:

0.612

Asia WGS

AF:

0.577

AC:

2006

AN:

3478

EpiCase

AF:

0.652

EpiControl

AF:

0.646

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

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

-0.58

CADD

Benign

1.8

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000016

dbscSNV1_RF

Benign

0.0

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