chr9-77300225-T-C

Variant names:

• chr9-77300225-T-C
• rs11145381
• NM_033305.3:c.3813-2690T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033305.3(VPS13A):​c.3813-2690T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,154 control chromosomes in the GnomAD database, including 3,782 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 (3782 hom., cov: 32)
• Consequence: VPS13A NM_033305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 0 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13A	NM_033305.3	MANE Select	c.3813-2690T>C		intron	N/A	NP_150648.2
	VPS13A	NM_001018037.2		c.3696-2690T>C		intron	N/A	NP_001018047.1
	VPS13A	NM_015186.4		c.3813-2690T>C		intron	N/A	NP_056001.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13A	ENST00000360280.8	TSL:1 MANE Select	c.3813-2690T>C		intron	N/A	ENSP00000353422.3
	VPS13A	ENST00000376636.7	TSL:1	c.3696-2690T>C		intron	N/A	ENSP00000365823.3
	VPS13A	ENST00000643348.1		c.3813-2690T>C		intron	N/A	ENSP00000493592.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29862 AN: 152036 Hom.: 3779 Cov.: 32

Gnomad AFR AF: 0.0495

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.196 AC: 29867 AN: 152154 Hom.: 3782 Cov.: 32 AF XY: 0.203 AC XY: 15118 AN XY: 74364

African (AFR) AF: 0.0494 AC: 2052 AN: 41552

American (AMR) AF: 0.338 AC: 5165 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 765 AN: 3466

East Asian (EAS) AF: 0.395 AC: 2043 AN: 5172

South Asian (SAS) AF: 0.300 AC: 1450 AN: 4826

European-Finnish (FIN) AF: 0.258 AC: 2727 AN: 10550

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14856 AN: 67994

Other (OTH) AF: 0.214 AC: 453 AN: 2112

Alfa AF: 0.107 Hom.: 172

Bravo AF: 0.197

Asia WGS AF: 0.328 AC: 1135 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.71
PhyloP100		1.3
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: rs11145381; hg19: chr9-79915141;