NM_033305.3:c.9C>G

Variant names:

• chr9-77177713-C-G
• NM_033305.3:c.9C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_033305.3(VPS13A):​c.9C>G​(p.Phe3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars). Synonymous variant affecting the same amino acid position (i.e. F3F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: VPS13A NM_033305.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.704
• 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-AS1 (HGNC:44167): (VPS13A antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13A	NM_033305.3	c.9C>G	p.Phe3Leu	missense_variant	Exon 1 of 72	ENST00000360280.8	NP_150648.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13A	ENST00000360280.8	c.9C>G	p.Phe3Leu	missense_variant	Exon 1 of 72	1	NM_033305.3	ENSP00000353422.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Chorea-acanthocytosis Uncertain:1

May 28, 2025

Natera, Inc.

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.73	.;.;D;.;.;.;D
Eigen	Benign	0.035
Eigen_PC	Benign	0.060
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.88	.;D;.;.;D;D;D
M_CAP	Pathogenic	0.76	D
MetaRNN	Uncertain	0.50	D;D;D;D;D;D;D
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	1.2	L;L;L;L;L;L;L
PhyloP100		0.70
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.9	D;D;D;D;.;.;.
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D;D;D;D;.;.;.
Sift4G	Benign	0.39	T;T;T;T;.;.;.
Polyphen		1.0	D;P;D;D;D;D;D
Vest4		0.54
MutPred		0.46		Gain of disorder (P = 0.1153);Gain of disorder (P = 0.1153);Gain of disorder (P = 0.1153);Gain of disorder (P = 0.1153);Gain of disorder (P = 0.1153);Gain of disorder (P = 0.1153);Gain of disorder (P = 0.1153);
MVP		0.73
MPC		4.0
ClinPred		0.99	D
GERP RS		4.0
PromoterAI		-0.044	Neutral
Varity_R		0.83
gMVP		0.80
Mutation Taster		=43/57	disease causing

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

hg19: chr9-79792629;