Genetic Variant VPS13A-AS1:n.244dupC (chr9-77177270-T-TG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The ENST00000721228.1(VPS13A-AS1):n.244dupC variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00802 in 193,280 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0091 ( 2 hom. )

Consequence

VPS13A-AS1
ENST00000721228.1 non_coding_transcript_exon

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.783

Publications

0 publications found

Variant links:

Genes affected

VPS13A-AS1 (HGNC:44167): (VPS13A antisense RNA 1)

VPS13A-AS1 links:

VPS13A (HGNC:1908): (vacuolar protein sorting 13 homolog A) The protein encoded by this gene may control steps in the cycling of proteins through the trans-Golgi network to endosomes, lysosomes and the plasma membrane. Mutations in this gene cause the autosomal recessive disorder, chorea-acanthocytosis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

VPS13A Gene-Disease associations (from GenCC):

chorea-acanthocytosis
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)

VPS13A links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 9-77177270-T-TG is Benign according to our data. Variant chr9-77177270-T-TG is described in ClinVar as [Likely_benign]. Clinvar id is 1703371.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00907 (373/41140) while in subpopulation MID AF = 0.0357 (6/168). AF 95% confidence interval is 0.0156. There are 2 homozygotes in GnomAdExome4. There are 171 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13A-AS1	NR_026668.2 link	n.291+356dupC		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
VPS13A-AS1	ENST00000721228.1 link	n.244dupC	non_coding_transcript_exon_variant	Exon 1 of 2
VPS13A-AS1	ENST00000721229.1 link	n.211dupC	non_coding_transcript_exon_variant	Exon 1 of 2
VPS13A-AS1	ENST00000721230.1 link	n.200dupC	non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00776

AC:

1179

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00293

Gnomad MID

AF:

0.0605

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.00862

GnomAD4 exome

AF:

0.00907

AC:

373

AN:

41140

Hom.:

AF XY:

0.00793

AC XY:

171

AN XY:

21564

show subpopulations

African (AFR)

AF:

0.00568

AC:

AN:

176

American (AMR)

AF:

0.0115

AC:

AN:

520

Ashkenazi Jewish (ASJ)

AF:

0.0138

AC:

AN:

798

East Asian (EAS)

AF:

0.00

AC:

AN:

378

South Asian (SAS)

AF:

0.00186

AC:

AN:

6986

European-Finnish (FIN)

AF:

0.00363

AC:

AN:

2756

Middle Eastern (MID)

AF:

0.0357

AC:

AN:

168

European-Non Finnish (NFE)

AF:

0.0111

AC:

299

AN:

26848

Other (OTH)

AF:

0.0108

AC:

AN:

2510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00774

AC:

1178

AN:

152140

Hom.:

Cov.:

AF XY:

0.00730

AC XY:

543

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.00250

AC:

104

AN:

41534

American (AMR)

AF:

0.00529

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5128

South Asian (SAS)

AF:

0.00291

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00293

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.0616

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0124

AC:

845

AN:

67986

Other (OTH)

AF:

0.00853

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

114

170

227

284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0104

Hom.:

Bravo

AF:

0.00830

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 16, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.78

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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9-77177270-T-TG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over