9-77177721-T-G

Variant names:

• chr9-77177721-T-G
• NM_033305.3:c.17T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_033305.3(VPS13A):​c.17T>G​(p.Val6Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: VPS13A NM_033305.3 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 5.00
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.935

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13A	NM_033305.3	c.17T>G	p.Val6Gly	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.17T>G	p.Val6Gly	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

Mar 30, 2025

Natera, Inc.

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.86	.;.;D;.;.;.;D
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.88	.;D;.;.;D;D;D
M_CAP	Pathogenic	0.85	D
MetaRNN	Pathogenic	0.94	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.59	D
MutationAssessor	Uncertain	2.7	M;M;M;M;M;M;M
PhyloP100		5.0
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-4.6	D;D;D;D;.;.;.
REVEL	Pathogenic	0.84
Sift	Uncertain	0.0020	D;D;D;D;.;.;.
Sift4G	Uncertain	0.0020	D;D;D;D;.;.;.
Polyphen		0.99	D;D;D;D;D;D;D
Vest4		0.40
MutPred		0.79		Loss of stability (P = 0.0035);Loss of stability (P = 0.0035);Loss of stability (P = 0.0035);Loss of stability (P = 0.0035);Loss of stability (P = 0.0035);Loss of stability (P = 0.0035);Loss of stability (P = 0.0035);
MVP		0.94
MPC		3.7
ClinPred		1.0	D
GERP RS		4.9
PromoterAI		-0.11	Neutral
Varity_R		0.94
gMVP		0.82
Mutation Taster		=55/45	polymorphism

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: chr9-79792637;