9-77294602-A-G

Variant names:

• chr9-77294602-A-G
• rs1574144
• NM_033305.3:c.3508-940A>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.3508-940A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,174 control chromosomes in the GnomAD database, including 2,885 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 0.19 (2885 hom., cov: 32)
• Consequence: VPS13A NM_033305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 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.3508-940A>G		intron	N/A	NP_150648.2
	VPS13A	NM_001018037.2		c.3391-940A>G		intron	N/A	NP_001018047.1
	VPS13A	NM_015186.4		c.3508-940A>G		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.3508-940A>G		intron	N/A	ENSP00000353422.3
	VPS13A	ENST00000376636.7	TSL:1	c.3391-940A>G		intron	N/A	ENSP00000365823.3
	VPS13A	ENST00000643348.1		c.3508-940A>G		intron	N/A	ENSP00000493592.1

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28641 AN: 152056 Hom.: 2880 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0339

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.188 AC: 28671 AN: 152174 Hom.: 2885 Cov.: 32 AF XY: 0.185 AC XY: 13757 AN XY: 74410

African (AFR) AF: 0.198 AC: 8229 AN: 41484

American (AMR) AF: 0.138 AC: 2103 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3468

East Asian (EAS) AF: 0.0339 AC: 176 AN: 5186

South Asian (SAS) AF: 0.209 AC: 1009 AN: 4824

European-Finnish (FIN) AF: 0.181 AC: 1923 AN: 10600

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14093 AN: 68000

Other (OTH) AF: 0.170 AC: 359 AN: 2114

Alfa AF: 0.203 Hom.: 535

Bravo AF: 0.184

Asia WGS AF: 0.112 AC: 391 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.45
PhyloP100		-0.033
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: rs1574144; hg19: chr9-79909518;