9-77177718-C-A

Variant names:

• chr9-77177718-C-A
• rs2131030007
• NM_033305.3:c.14C>A

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_033305.3(VPS13A):​c.14C>A​(p.Ser5*) variant causes a stop gained 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 Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: VPS13A NM_033305.3 stop_gained
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 6.58
• 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: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 306 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-77177718-C-A is Pathogenic according to our data. Variant chr9-77177718-C-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 1325340.Status of the report is criteria_provided_single_submitter, 1 stars.

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.14C>A	p.Ser5*	stop_gained	Exon 1 of 72	NP_150648.2	Q96RL7-1
	VPS13A	NM_001018037.2		c.14C>A	p.Ser5*	stop_gained	Exon 1 of 71	NP_001018047.1	Q96RL7-3
	VPS13A	NM_015186.4		c.14C>A	p.Ser5*	stop_gained	Exon 1 of 69	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.14C>A	p.Ser5*	stop_gained	Exon 1 of 72	ENSP00000353422.3	Q96RL7-1
	VPS13A	ENST00000376636.7	TSL:1	c.14C>A	p.Ser5*	stop_gained	Exon 1 of 71	ENSP00000365823.3	Q96RL7-3
	VPS13A	ENST00000643348.1		c.14C>A	p.Ser5*	stop_gained	Exon 1 of 69	ENSP00000493592.1	Q96RL7-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Chorea-acanthocytosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.60
CADD	Pathogenic	41
DANN	Uncertain	0.99
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.82	D
PhyloP100		6.6
Vest4		0.60
GERP RS		4.9
PromoterAI		-0.058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=0/200	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs2131030007; hg19: chr9-79792634;