Variant 2-63912336-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_016516.3(VPS54):c.2625+9T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00545 in 1,597,064 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0046 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0055 ( 41 hom. )

Consequence

VPS54
NM_016516.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.406

Variant links:

Genes affected

VPS54 (HGNC:18652): (VPS54 subunit of GARP complex) This gene encodes for a protein that in yeast forms part of a trimeric vacuolar-protein-sorting complex that is required for retrograde transport of proteins from prevacuoles to the late Golgi compartment. As in yeast, mammalian Vps54 proteins contain a coiled-coil region and dileucine motifs. Alternative splicing results in multiple transcript variants encoding different isoforms [provided by RefSeq, Jul 2008]

VPS54 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-63912336-A-T is Benign according to our data. Variant chr2-63912336-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1209896.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-63912336-A-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00554 (8002/1444744) while in subpopulation MID AF= 0.0234 (121/5164). AF 95% confidence interval is 0.02. There are 41 homozygotes in gnomad4_exome. There are 4084 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High AC in GnomAd4 at 707 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS54	NM_016516.3 link	c.2625+9T>A		intron_variant	Intron 20 of 22	ENST00000272322.9	NP_057600.2	Q9P1Q0-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
VPS54	ENST00000272322.9 link	c.2625+9T>A	intron_variant	Intron 20 of 22	5	NM_016516.3	ENSP00000272322.4	Q9P1Q0-1
VPS54	ENST00000409558.8 link	c.2589+9T>A	intron_variant	Intron 20 of 22	1		ENSP00000386980.3	Q9P1Q0-4
VPS54	ENST00000354504.7 link	c.2166+9T>A	intron_variant	Intron 17 of 19	1		ENSP00000346499.3	Q9P1Q0-3
VPS54	ENST00000416400.1 link	n.*365+9T>A	intron_variant	Intron 7 of 9	1		ENSP00000414725.2	A0A0A0MT48

Frequencies

GnomAD3 genomes

AF:

0.00464

AC:

706

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.00779

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00678

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00486

AC:

1151

AN:

236674

Hom.:

AF XY:

0.00538

AC XY:

689

AN XY:

128176

show subpopulations

Gnomad AFR exome

AF:

0.000549

Gnomad AMR exome

AF:

0.00375

Gnomad ASJ exome

AF:

0.00768

Gnomad EAS exome

AF:

0.0000558

Gnomad SAS exome

AF:

0.00523

Gnomad FIN exome

AF:

0.000995

Gnomad NFE exome

AF:

0.00682

Gnomad OTH exome

AF:

0.00861

GnomAD4 exome

AF:

0.00554

AC:

8002

AN:

1444744

Hom.:

Cov.:

AF XY:

0.00569

AC XY:

4084

AN XY:

718350

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00384

Gnomad4 ASJ exome

AF:

0.00709

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00532

Gnomad4 FIN exome

AF:

0.00106

Gnomad4 NFE exome

AF:

0.00600

Gnomad4 OTH exome

AF:

0.00623

GnomAD4 genome

AF:

0.00464

AC:

707

AN:

152320

Hom.:

Cov.:

AF XY:

0.00440

AC XY:

328

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00601

Gnomad4 ASJ

AF:

0.00779

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00678

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00707

Hom.:

Bravo

AF:

0.00435

Asia WGS

AF:

0.00462

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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