9-77276321-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_033305.3(VPS13A):c.2824+100T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,115,318 control chromosomes in the GnomAD database, including 24,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3523 hom., cov: 32)
  • Exomes 𝑓: 0.20 (21412 hom.)
• Consequence: VPS13A NM_033305.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.124

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-77276321-T-G is Benign according to our data. Variant chr9-77276321-T-G is described in ClinVar as [Benign]. Clinvar id is 1228232.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VPS13A	NM_033305.3	c.2824+100T>G		intron_variant		ENST00000360280.8
VPS13A	NM_001018037.2	c.2824+100T>G		intron_variant
VPS13A	NM_001018038.3	c.2824+100T>G		intron_variant
VPS13A	NM_015186.4	c.2824+100T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS13A	ENST00000360280.8	c.2824+100T>G		intron_variant		1	NM_033305.3	P4
VPS13A	ENST00000376636.7	c.2824+100T>G		intron_variant		1
VPS13A	ENST00000643348.1	c.2824+100T>G		intron_variant
VPS13A	ENST00000645632.1	c.2824+100T>G		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31513 AN: 152032 Hom.: 3516 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0333

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.205 AC: 197086 AN: 963168 Hom.: 21412 AF XY: 0.205 AC XY: 98632 AN XY: 481392

Gnomad4 AFR exome AF: 0.263

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.0291

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.207 AC: 31545 AN: 152150 Hom.: 3523 Cov.: 32 AF XY: 0.203 AC XY: 15114 AN XY: 74412

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.0333

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.187

Alfa AF: 0.191 Hom.: 1376

Bravo AF: 0.206

Asia WGS AF: 0.118 AC: 411 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.9
Dann	Benign	0.63

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: rs7030802; hg19: chr9-79891237;