9-77177270-T-TG

Variant names:

• chr9-77177270-T-TG
• rs201549198
• ENST00000644612.1:n.554+356_554+357insC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NR_026668.2(VPS13A-AS1):​n.291+356dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00802 in 193,280 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0077 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0091 (2 hom.)
• Consequence: VPS13A-AS1 NR_026668.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.783

Genes affected

VPS13A-AS1 (HGNC:44167): (VPS13A antisense RNA 1)

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 -10 ACMG points.

• BP6: Variant 9-77177270-T-TG is Benign according to our data. Variant chr9-77177270-T-TG is described in ClinVar as [Likely_benign]. Clinvar id is 1703371.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00907 (373/41140) while in subpopulation MID AF= 0.0357 (6/168). AF 95% confidence interval is 0.0156. There are 2 homozygotes in gnomad4_exome. There are 171 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13A-AS1	NR_026668.2	n.291+356dupC		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13A-AS1	ENST00000644612.1	n.554+356_554+357insC		intron_variant	Intron 1 of 1
VPS13A	ENST00000376636.7	c.-435_-434insG		upstream_gene_variant		1		ENSP00000365823.3

Frequencies

GnomAD3 genomes AF: 0.00776 AC: 1179 AN: 152022 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00251

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00293

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.00862

GnomAD4 exome AF: 0.00907 AC: 373 AN: 41140 Hom.: 2 AF XY: 0.00793 AC XY: 171 AN XY: 21564

Gnomad4 AFR exome AF: 0.00568

Gnomad4 AMR exome AF: 0.0115

Gnomad4 ASJ exome AF: 0.0138

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00186

Gnomad4 FIN exome AF: 0.00363

Gnomad4 NFE exome AF: 0.0111

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.00774 AC: 1178 AN: 152140 Hom.: 6 Cov.: 33 AF XY: 0.00730 AC XY: 543 AN XY: 74372

Gnomad4 AFR AF: 0.00250

Gnomad4 AMR AF: 0.00529

Gnomad4 ASJ AF: 0.0184

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00291

Gnomad4 FIN AF: 0.00293

Gnomad4 NFE AF: 0.0124

Gnomad4 OTH AF: 0.00853

Alfa AF: 0.0104 Hom.: 0

Bravo AF: 0.00830

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 16, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201549198; hg19: chr9-79792186;