dbSNP rs2150901: VPS13A:c.555+466A>G (chr9-77211141-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_033305.3(VPS13A):c.555+466A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 158,330 control chromosomes in the GnomAD database, including 3,462 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3355 hom., cov: 32)

Exomes 𝑓: 0.18 ( 107 hom. )

Consequence

VPS13A
NM_033305.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.403

Publications

1 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 Gene-Disease associations (from GenCC):

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

VPS13A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033305.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VPS13A	NM_033305.3	MANE Select	c.555+466A>G	intron	N/A	NP_150648.2	Q96RL7-1
VPS13A	NM_001018037.2		c.555+466A>G	intron	N/A	NP_001018047.1	Q96RL7-3
VPS13A	NM_015186.4		c.555+466A>G	intron	N/A	NP_056001.1	Q96RL7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VPS13A	ENST00000360280.8	TSL:1 MANE Select	c.555+466A>G	intron	N/A	ENSP00000353422.3	Q96RL7-1
VPS13A	ENST00000376636.7	TSL:1	c.555+466A>G	intron	N/A	ENSP00000365823.3	Q96RL7-3
VPS13A	ENST00000643348.1		c.555+466A>G	intron	N/A	ENSP00000493592.1	Q96RL7-2

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30918

AN:

151992

Hom.:

3345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.0562

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.184

GnomAD4 exome

AF:

0.179

AC:

1111

AN:

6220

Hom.:

107

AF XY:

0.183

AC XY:

659

AN XY:

3592

show subpopulations

African (AFR)

AF:

0.190

AC:

AN:

American (AMR)

AF:

0.133

AC:

104

AN:

782

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

AN:

East Asian (EAS)

AF:

0.0299

AC:

AN:

368

South Asian (SAS)

AF:

0.234

AC:

153

AN:

654

European-Finnish (FIN)

AF:

0.118

AC:

AN:

110

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

European-Non Finnish (NFE)

AF:

0.195

AC:

773

AN:

3962

Other (OTH)

AF:

0.188

AC:

AN:

208

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

131

174

218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.204

AC:

30964

AN:

152110

Hom.:

3355

Cov.:

AF XY:

0.199

AC XY:

14822

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.248

AC:

10278

AN:

41506

American (AMR)

AF:

0.162

AC:

2471

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

595

AN:

3468

East Asian (EAS)

AF:

0.0568

AC:

294

AN:

5180

South Asian (SAS)

AF:

0.223

AC:

1074

AN:

4826

European-Finnish (FIN)

AF:

0.162

AC:

1715

AN:

10568

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.206

AC:

13979

AN:

67972

Other (OTH)

AF:

0.182

AC:

383

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1257

2514

3771

5028

6285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.214

Hom.:

544

Bravo

AF:

0.204

Asia WGS

AF:

0.136

AC:

475

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.24

(source)

DANN

Benign

0.45

PhyloP100

-0.40

Mutation Taster

=100/0

polymorphism (auto)

(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