rs11145323

Variant names:

• chr9-77183920-A-G
• rs11145323
• NM_033305.3:c.100+6116A>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.100+6116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,180 control chromosomes in the GnomAD database, including 3,379 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 (3379 hom., cov: 33)
• Consequence: VPS13A NM_033305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13A	NM_033305.3	c.100+6116A>G		intron_variant	Intron 1 of 71	ENST00000360280.8	NP_150648.2
VPS13A	NM_001018037.2	c.100+6116A>G		intron_variant	Intron 1 of 70		NP_001018047.1
VPS13A	NM_015186.4	c.100+6116A>G		intron_variant	Intron 1 of 68		NP_056001.1
VPS13A	NM_001018038.3	c.100+6116A>G		intron_variant	Intron 1 of 68		NP_001018048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13A	ENST00000360280.8	c.100+6116A>G		intron_variant	Intron 1 of 71	1	NM_033305.3	ENSP00000353422.3
VPS13A	ENST00000376636.7	c.100+6116A>G		intron_variant	Intron 1 of 70	1		ENSP00000365823.3
VPS13A	ENST00000643348.1	c.100+6116A>G		intron_variant	Intron 1 of 68			ENSP00000493592.1
VPS13A	ENST00000645632.1	c.100+6116A>G		intron_variant	Intron 1 of 68			ENSP00000496361.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 31088 AN: 152062 Hom.: 3368 Cov.: 33

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0563

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.205 AC: 31135 AN: 152180 Hom.: 3379 Cov.: 33 AF XY: 0.200 AC XY: 14892 AN XY: 74402

African (AFR) AF: 0.252 AC: 10453 AN: 41502

American (AMR) AF: 0.162 AC: 2476 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3468

East Asian (EAS) AF: 0.0569 AC: 295 AN: 5188

South Asian (SAS) AF: 0.222 AC: 1071 AN: 4828

European-Finnish (FIN) AF: 0.163 AC: 1723 AN: 10598

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13945 AN: 67990

Other (OTH) AF: 0.184 AC: 388 AN: 2114

Alfa AF: 0.213 Hom.: 566

Bravo AF: 0.206

Asia WGS AF: 0.138 AC: 481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.58
PhyloP100		0.33
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: rs11145323; hg19: chr9-79798836;