9-77334940-C-T

Variant names:

• chr9-77334940-C-T
• rs11145388
• NM_033305.3:c.6096-2315C>T

Variant summary

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

The NM_033305.3(VPS13A):​c.6096-2315C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,052 control chromosomes in the GnomAD database, including 2,836 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 0.17 (2836 hom., cov: 32)
• Consequence: VPS13A NM_033305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, Orphanet

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 = 0.375 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.6096-2315C>T		intron	N/A	NP_150648.2	Q96RL7-1
	VPS13A	NM_001018037.2		c.5979-2315C>T		intron	N/A	NP_001018047.1	Q96RL7-3
	VPS13A	NM_015186.4		c.6096-2315C>T		intron	N/A	NP_056001.1	Q96RL7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13A	ENST00000360280.8	TSL:1 MANE Select	c.6096-2315C>T		intron	N/A	ENSP00000353422.3	Q96RL7-1
	VPS13A	ENST00000376636.7	TSL:1	c.5979-2315C>T		intron	N/A	ENSP00000365823.3	Q96RL7-3
	VPS13A	ENST00000419472.1	TSL:1	c.852-2315C>T		intron	N/A	ENSP00000414410.1	H0Y7P8

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26117 AN: 151936 Hom.: 2837 Cov.: 32

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.172 AC: 26113 AN: 152052 Hom.: 2836 Cov.: 32 AF XY: 0.179 AC XY: 13291 AN XY: 74312

African (AFR) AF: 0.0536 AC: 2225 AN: 41498

American (AMR) AF: 0.270 AC: 4131 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 694 AN: 3470

East Asian (EAS) AF: 0.389 AC: 2003 AN: 5148

South Asian (SAS) AF: 0.285 AC: 1374 AN: 4822

European-Finnish (FIN) AF: 0.224 AC: 2365 AN: 10562

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12577 AN: 67960

Other (OTH) AF: 0.194 AC: 410 AN: 2114

Alfa AF: 0.188 Hom.: 1529

Bravo AF: 0.171

Asia WGS AF: 0.315 AC: 1093 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.6
DANN	Benign	0.61
PhyloP100		-0.52
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: rs11145388; hg19: chr9-79949856;