rs2150901

chr9-77211141-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS13A	NM_033305.3	c.555+466A>G		intron_variant		ENST00000360280.8
VPS13A	NM_001018037.2	c.555+466A>G		intron_variant
VPS13A	NM_001018038.3	c.555+466A>G		intron_variant
VPS13A	NM_015186.4	c.555+466A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS13A	ENST00000360280.8	c.555+466A>G		intron_variant		1	NM_033305.3	P4

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30918 AN: 151992 Hom.: 3345 Cov.: 32

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

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.113

Gnomad4 EAS exome AF: 0.0299

Gnomad4 SAS exome AF: 0.234

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.204 AC: 30964 AN: 152110 Hom.: 3355 Cov.: 32 AF XY: 0.199 AC XY: 14822 AN XY: 74366

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.0568

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.182

Alfa AF: 0.212 Hom.: 516

Bravo AF: 0.204

Asia WGS AF: 0.136 AC: 475 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.24
Dann	Benign	0.45

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: rs2150901; hg19: chr9-79826057;