16-70762513-T-A

Variant names:

• chr16-70762513-T-A
• rs16970522
• NM_018052.5:c.1371+27A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018052.5(VAC14):​c.1371+27A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00377 in 1,612,220 control chromosomes in the GnomAD database, including 186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (91 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (95 hom.)
• Consequence: VAC14 NM_018052.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.777
• Publications: 2 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-AS1 (HGNC:48605): (VAC14 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-70762513-T-A is Benign according to our data. Variant chr16-70762513-T-A is described in ClinVar as Benign. ClinVar VariationId is 1282718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0619 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAC14	NM_018052.5	MANE Select	c.1371+27A>T		intron	N/A	NP_060522.3
	VAC14	NM_001351157.2		c.669+27A>T		intron	N/A	NP_001338086.1
	VAC14-AS1	NR_034083.3		n.336+1255T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAC14	ENST00000261776.10	TSL:1 MANE Select	c.1371+27A>T		intron	N/A	ENSP00000261776.5	Q08AM6-1
	VAC14-AS1	ENST00000562507.5	TSL:1	n.333+1255T>A		intron	N/A
	VAC14	ENST00000568548.5	TSL:1	n.*1097+27A>T		intron	N/A	ENSP00000454650.1	H3BN23

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2884 AN: 152164 Hom.: 94 Cov.: 32

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0101

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0172

GnomAD2 exomes AF: 0.00518 AC: 1297 AN: 250450 AF XY: 0.00387

Gnomad AFR exome AF: 0.0659

Gnomad AMR exome AF: 0.00432

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000521

Gnomad OTH exome AF: 0.00295

GnomAD4 exome AF: 0.00219 AC: 3199 AN: 1459938 Hom.: 95 Cov.: 29 AF XY: 0.00194 AC XY: 1407 AN XY: 726370

African (AFR) AF: 0.0684 AC: 2288 AN: 33434

American (AMR) AF: 0.00441 AC: 197 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39680

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86120

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53380

Middle Eastern (MID) AF: 0.00954 AC: 55 AN: 5764

European-Non Finnish (NFE) AF: 0.000296 AC: 329 AN: 1110408

Other (OTH) AF: 0.00519 AC: 313 AN: 60346

GnomAD4 genome AF: 0.0189 AC: 2884 AN: 152282 Hom.: 91 Cov.: 32 AF XY: 0.0192 AC XY: 1428 AN XY: 74464

African (AFR) AF: 0.0640 AC: 2658 AN: 41562

American (AMR) AF: 0.0101 AC: 154 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 68026

Other (OTH) AF: 0.0170 AC: 36 AN: 2114

Alfa AF: 0.00936 Hom.: 11

Bravo AF: 0.0217

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.56
DANN	Benign	0.53
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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

Other links and lift over

dbSNP: rs16970522; hg19: chr16-70796416;