rs11145410

Positions:

• chr9-77397484-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033305.3(VPS13A):​c.9190-5752G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,024 control chromosomes in the GnomAD database, including 2,795 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 0.17 (2795 hom., cov: 32)
• Consequence: VPS13A NM_033305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS13A	NM_033305.3	c.9190-5752G>A		intron_variant		ENST00000360280.8
VPS13A	NM_001018037.2	c.9073-5752G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS13A	ENST00000360280.8	c.9190-5752G>A		intron_variant		1	NM_033305.3	P4
VPS13A	ENST00000376636.7	c.9073-5752G>A		intron_variant		1
VPS13A	ENST00000376646.3	n.307+1616G>A		intron_variant, non_coding_transcript_variant		5
VPS13A	ENST00000484581.6	n.433-5752G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25909 AN: 151906 Hom.: 2795 Cov.: 32

Gnomad AFR AF: 0.0443

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.170 AC: 25909 AN: 152024 Hom.: 2795 Cov.: 32 AF XY: 0.177 AC XY: 13135 AN XY: 74292

Gnomad4 AFR AF: 0.0443

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.194

Alfa AF: 0.177 Hom.: 522

Bravo AF: 0.170

Asia WGS AF: 0.280 AC: 972 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs11145410; hg19: chr9-80012400;