Genetic Variant VPS13A:c.-183G>A (chr9-77177522-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000376636.7(VPS13A):c.-183G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000617 in 599,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

VPS13A
ENST00000376636.7 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.100

Publications

5 publications found

Variant links:

Genes affected

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 links:

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

VPS13A-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000376636.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VPS13A-AS1	NR_026668.2		n.291+105C>T	intron	N/A
VPS13A	NM_033305.3	MANE Select	c.-183G>A	upstream_gene	N/A	NP_150648.2	Q96RL7-1
VPS13A	NM_001018037.2		c.-183G>A	upstream_gene	N/A	NP_001018047.1	Q96RL7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VPS13A	ENST00000376636.7	TSL:1	c.-183G>A	5_prime_UTR_premature_start_codon_gain	Exon 1 of 71	ENSP00000365823.3	Q96RL7-3
VPS13A	ENST00000376636.7	TSL:1	c.-183G>A	5_prime_UTR	Exon 1 of 71	ENSP00000365823.3	Q96RL7-3
VPS13A-AS1	ENST00000644612.2		n.575+105C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000967

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.0000581

AC:

AN:

447340

Hom.:

Cov.:

AF XY:

0.0000626

AC XY:

AN XY:

239764

show subpopulations

African (AFR)

AF:

0.0000851

AC:

AN:

11746

American (AMR)

AF:

0.00

AC:

AN:

24188

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13600

East Asian (EAS)

AF:

0.000540

AC:

AN:

27772

South Asian (SAS)

AF:

0.0000994

AC:

AN:

50324

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1926

European-Non Finnish (NFE)

AF:

0.0000113

AC:

AN:

265714

Other (OTH)

AF:

0.0000805

AC:

AN:

24834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.554

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41414

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000967

AC:

AN:

5172

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67980

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000626

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Chorea-acanthocytosis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.9

(source)

DANN

Benign

0.89

PhyloP100

-0.10

PromoterAI

0.17

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over