Genetic Variant VPS13A:c.-181G>A (chr9-77177524-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000376636.7(VPS13A):c.-181G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 604,510 control chromosomes in the GnomAD database, including 6,267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1209 hom., cov: 33)

Exomes 𝑓: 0.14 ( 5058 hom. )

Consequence

VPS13A
ENST00000376636.7 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0420

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

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

BP6

Variant 9-77177524-G-A is Benign according to our data. Variant chr9-77177524-G-A is described in ClinVar as Benign. ClinVar VariationId is 367338.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

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+103C>T	intron	N/A
VPS13A	NM_033305.3	MANE Select	c.-181G>A	upstream_gene	N/A	NP_150648.2	Q96RL7-1
VPS13A	NM_001018037.2		c.-181G>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.-181G>A	5_prime_UTR	Exon 1 of 71	ENSP00000365823.3	Q96RL7-3
VPS13A-AS1	ENST00000644612.2		n.575+103C>T	intron	N/A
VPS13A-AS1	ENST00000721227.1		n.266+103C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16332

AN:

152128

Hom.:

1207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0295

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.0992

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.00232

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.0896

Gnomad MID

AF:

0.205

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.132

GnomAD4 exome

AF:

0.137

AC:

62166

AN:

452266

Hom.:

5058

Cov.:

AF XY:

0.141

AC XY:

34207

AN XY:

242514

show subpopulations

African (AFR)

AF:

0.0276

AC:

331

AN:

12014

American (AMR)

AF:

0.0807

AC:

1972

AN:

24448

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

2554

AN:

13734

East Asian (EAS)

AF:

0.000391

AC:

AN:

28146

South Asian (SAS)

AF:

0.181

AC:

9175

AN:

50652

European-Finnish (FIN)

AF:

0.101

AC:

2772

AN:

27534

Middle Eastern (MID)

AF:

0.177

AC:

341

AN:

1926

European-Non Finnish (NFE)

AF:

0.155

AC:

41627

AN:

268762

Other (OTH)

AF:

0.135

AC:

3383

AN:

25050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

2744

5488

8233

10977

13721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

234

468

702

936

1170

<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:

0.107

AC:

16328

AN:

152244

Hom.:

1209

Cov.:

AF XY:

0.105

AC XY:

7821

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0294

AC:

1224

AN:

41568

American (AMR)

AF:

0.0989

AC:

1514

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

627

AN:

3470

East Asian (EAS)

AF:

0.00213

AC:

AN:

5166

South Asian (SAS)

AF:

0.168

AC:

812

AN:

4826

European-Finnish (FIN)

AF:

0.0896

AC:

950

AN:

10604

Middle Eastern (MID)

AF:

0.200

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.157

AC:

10668

AN:

67990

Other (OTH)

AF:

0.130

AC:

274

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

744

1489

2233

2978

3722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<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:

0.129

Hom.:

193

Bravo

AF:

0.103

Asia WGS

AF:

0.0690

AC:

241

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Chorea-acanthocytosis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

9.0

(source)

DANN

Benign

0.89

PhyloP100

0.042

PromoterAI

0.055

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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