rs2150901

Variant names:

• chr9-77211141-A-G
• rs2150901
• NM_033305.3:c.555+466A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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)

ACMG classification

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

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

Ensembl Transcripts

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

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

African (AFR) AF: 0.190 AC: 8 AN: 42

American (AMR) AF: 0.133 AC: 104 AN: 782

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 9 AN: 80

East Asian (EAS) AF: 0.0299 AC: 11 AN: 368

South Asian (SAS) AF: 0.234 AC: 153 AN: 654

European-Finnish (FIN) AF: 0.118 AC: 13 AN: 110

Middle Eastern (MID) AF: 0.0714 AC: 1 AN: 14

European-Non Finnish (NFE) AF: 0.195 AC: 773 AN: 3962

Other (OTH) AF: 0.188 AC: 39 AN: 208

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

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: 75 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 13979 AN: 67972

Other (OTH) AF: 0.182 AC: 383 AN: 2108

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
DANN	Benign	0.45
PhyloP100		-0.40
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

Other links and lift over

dbSNP: rs2150901; hg19: chr9-79826057;