rs17423381

Variant names:

• chr9-77302744-C-G
• rs17423381
• NM_033305.3:c.3813-171C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033305.3(VPS13A):​c.3813-171C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0575 in 152,118 control chromosomes in the GnomAD database, including 372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.057 (372 hom., cov: 31)
• Consequence: VPS13A NM_033305.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.666
• Publications: 1 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 9-77302744-C-G is Benign according to our data. Variant chr9-77302744-C-G is described in ClinVar as Benign. ClinVar VariationId is 1185291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.114 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13A	NM_033305.3	MANE Select	c.3813-171C>G		intron	N/A	NP_150648.2	Q96RL7-1
	VPS13A	NM_001018037.2		c.3696-171C>G		intron	N/A	NP_001018047.1	Q96RL7-3
	VPS13A	NM_015186.4		c.3813-171C>G		intron	N/A	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.3813-171C>G		intron	N/A	ENSP00000353422.3	Q96RL7-1
	VPS13A	ENST00000376636.7	TSL:1	c.3696-171C>G		intron	N/A	ENSP00000365823.3	Q96RL7-3
	VPS13A	ENST00000643348.1		c.3813-171C>G		intron	N/A	ENSP00000493592.1	Q96RL7-2

Frequencies

GnomAD3 genomes AF: 0.0575 AC: 8746 AN: 152000 Hom.: 371 Cov.: 31

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0571

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0853

Gnomad OTH AF: 0.0574

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

GnomAD4 genome AF: 0.0575 AC: 8742 AN: 152118 Hom.: 372 Cov.: 31 AF XY: 0.0566 AC XY: 4211 AN XY: 74370

African (AFR) AF: 0.0154 AC: 638 AN: 41492

American (AMR) AF: 0.0463 AC: 708 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0579 AC: 201 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5178

South Asian (SAS) AF: 0.122 AC: 590 AN: 4824

European-Finnish (FIN) AF: 0.0571 AC: 603 AN: 10562

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0854 AC: 5803 AN: 67988

Other (OTH) AF: 0.0563 AC: 119 AN: 2112

Alfa AF: 0.0685 Hom.: 56

Bravo AF: 0.0540

Asia WGS AF: 0.0490 AC: 172 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Chorea-acanthocytosis (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.3
DANN	Benign	0.78
PhyloP100		-0.67
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: rs17423381; hg19: chr9-79917660;