chr9-77289640-T-C

Variant summary

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

The NM_033305.3(VPS13A):​c.3340-3701T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 152,028 control chromosomes in the GnomAD database, including 28,868 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 0.61 ( 28868 hom., cov: 32)

Consequence

VPS13A
NM_033305.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.260

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: Orphanet, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)

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=-0.98).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VPS13ANM_033305.3 linkc.3340-3701T>C intron_variant Intron 31 of 71 ENST00000360280.8 NP_150648.2 Q96RL7-1
VPS13ANM_001018037.2 linkc.3223-3701T>C intron_variant Intron 30 of 70 NP_001018047.1 Q96RL7-3
VPS13ANM_015186.4 linkc.3340-3701T>C intron_variant Intron 31 of 68 NP_056001.1 Q96RL7-2
VPS13ANM_001018038.3 linkc.3340-3701T>C intron_variant Intron 31 of 68 NP_001018048.1 Q96RL7-4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VPS13AENST00000360280.8 linkc.3340-3701T>C intron_variant Intron 31 of 71 1 NM_033305.3 ENSP00000353422.3 Q96RL7-1

Frequencies

GnomAD3 genomes
AF:
0.608
AC:
92395
AN:
151910
Hom.:
28815
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.742
Gnomad AMI
AF:
0.603
Gnomad AMR
AF:
0.642
Gnomad ASJ
AF:
0.578
Gnomad EAS
AF:
0.686
Gnomad SAS
AF:
0.648
Gnomad FIN
AF:
0.494
Gnomad MID
AF:
0.595
Gnomad NFE
AF:
0.530
Gnomad OTH
AF:
0.604
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.609
AC:
92512
AN:
152028
Hom.:
28868
Cov.:
32
AF XY:
0.609
AC XY:
45232
AN XY:
74278
show subpopulations
African (AFR)
AF:
0.742
AC:
30795
AN:
41484
American (AMR)
AF:
0.642
AC:
9808
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.578
AC:
2008
AN:
3472
East Asian (EAS)
AF:
0.686
AC:
3547
AN:
5170
South Asian (SAS)
AF:
0.648
AC:
3118
AN:
4814
European-Finnish (FIN)
AF:
0.494
AC:
5207
AN:
10532
Middle Eastern (MID)
AF:
0.599
AC:
176
AN:
294
European-Non Finnish (NFE)
AF:
0.530
AC:
36033
AN:
67956
Other (OTH)
AF:
0.603
AC:
1270
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1760
3519
5279
7038
8798
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
762
1524
2286
3048
3810
<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:
0.560
Hom.:
12372
Bravo
AF:
0.624
Asia WGS
AF:
0.651
AC:
2261
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.98
CADD
Benign
2.2
DANN
Benign
0.71
PhyloP100
-0.26
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs7864334; hg19: chr9-79904556; API