rs17423381

Positions:

• chr9-77302744-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033305.3(VPS13A):​c.3813-171C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0575 in 152,118 control chromosomes in the GnomAD database, including 372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.057 (372 hom., cov: 31)
• Consequence: VPS13A NM_033305.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.666

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 9-77302744-C-G is Benign according to our data. Variant chr9-77302744-C-G is described in ClinVar as [Benign]. Clinvar id is 1185291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS13A	NM_033305.3	c.3813-171C>G		intron_variant		ENST00000360280.8
VPS13A	NM_001018037.2	c.3696-171C>G		intron_variant
VPS13A	NM_001018038.3	c.3813-171C>G		intron_variant
VPS13A	NM_015186.4	c.3813-171C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS13A	ENST00000360280.8	c.3813-171C>G		intron_variant		1	NM_033305.3	P4

Frequencies

GnomAD3 genomes AF: 0.0575 AC: 8746 AN: 152000 Hom.: 371 Cov.: 31

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0571

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0853

Gnomad OTH AF: 0.0574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0575 AC: 8742 AN: 152118 Hom.: 372 Cov.: 31 AF XY: 0.0566 AC XY: 4211 AN XY: 74370

Gnomad4 AFR AF: 0.0154

Gnomad4 AMR AF: 0.0463

Gnomad4 ASJ AF: 0.0579

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0571

Gnomad4 NFE AF: 0.0854

Gnomad4 OTH AF: 0.0563

Alfa AF: 0.0685 Hom.: 56

Bravo AF: 0.0540

Asia WGS AF: 0.0490 AC: 172 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Chorea-acanthocytosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.3
DANN	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs17423381; hg19: chr9-79917660;