9-77273480-A-G

Position:

• chr9-77273480-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000360280.8(VPS13A):​c.2512+116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 840,960 control chromosomes in the GnomAD database, including 275,494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (54685 hom., cov: 31)
  • Exomes 𝑓: 0.80 (220809 hom.)
• Consequence: VPS13A ENST00000360280.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.71

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 9-77273480-A-G is Benign according to our data. Variant chr9-77273480-A-G is described in ClinVar as [Benign]. Clinvar id is 1185286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS13A	NM_033305.3	c.2512+116A>G		intron_variant		ENST00000360280.8	NP_150648.2
VPS13A	NM_001018037.2	c.2512+116A>G		intron_variant			NP_001018047.1
VPS13A	NM_001018038.3	c.2512+116A>G		intron_variant			NP_001018048.1
VPS13A	NM_015186.4	c.2512+116A>G		intron_variant			NP_056001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13A	ENST00000360280.8	c.2512+116A>G		intron_variant		1	NM_033305.3	ENSP00000353422	P4
VPS13A	ENST00000376636.7	c.2512+116A>G		intron_variant		1		ENSP00000365823
VPS13A	ENST00000643348.1	c.2512+116A>G		intron_variant				ENSP00000493592
VPS13A	ENST00000645632.1	c.2512+116A>G		intron_variant				ENSP00000496361	A1

Frequencies

GnomAD3 genomes AF: 0.843 AC: 128230 AN: 152026 Hom.: 54637 Cov.: 31

Gnomad AFR AF: 0.962

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.837

GnomAD4 exome AF: 0.799 AC: 550201 AN: 688816 Hom.: 220809 AF XY: 0.799 AC XY: 287017 AN XY: 359000

Gnomad4 AFR exome AF: 0.967

Gnomad4 AMR exome AF: 0.888

Gnomad4 ASJ exome AF: 0.864

Gnomad4 EAS exome AF: 0.876

Gnomad4 SAS exome AF: 0.855

Gnomad4 FIN exome AF: 0.733

Gnomad4 NFE exome AF: 0.778

Gnomad4 OTH exome AF: 0.815

GnomAD4 genome AF: 0.844 AC: 128338 AN: 152144 Hom.: 54685 Cov.: 31 AF XY: 0.843 AC XY: 62729 AN XY: 74368

Gnomad4 AFR AF: 0.962

Gnomad4 AMR AF: 0.873

Gnomad4 ASJ AF: 0.868

Gnomad4 EAS AF: 0.880

Gnomad4 SAS AF: 0.860

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.778

Gnomad4 OTH AF: 0.834

Alfa AF: 0.804 Hom.: 10619

Bravo AF: 0.859

Asia WGS AF: 0.859 AC: 2989 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Chorea-acanthocytosis Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2050831; hg19: chr9-79888396;