chr9-77273480-A-G

Variant names:

• chr9-77273480-A-G
• rs2050831
• NM_033305.3:c.2512+116A>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.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 NM_033305.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.71
• Publications: 4 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: Orphanet, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
VPS13A	NM_033305.3	c.2512+116A>G		intron_variant	Intron 24 of 71	ENST00000360280.8	NP_150648.2
VPS13A	NM_001018037.2	c.2512+116A>G		intron_variant	Intron 24 of 70		NP_001018047.1
VPS13A	NM_015186.4	c.2512+116A>G		intron_variant	Intron 24 of 68		NP_056001.1
VPS13A	NM_001018038.3	c.2512+116A>G		intron_variant	Intron 24 of 68		NP_001018048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13A	ENST00000360280.8	c.2512+116A>G		intron_variant	Intron 24 of 71	1	NM_033305.3	ENSP00000353422.3
VPS13A	ENST00000376636.7	c.2512+116A>G		intron_variant	Intron 24 of 70	1		ENSP00000365823.3
VPS13A	ENST00000643348.1	c.2512+116A>G		intron_variant	Intron 24 of 68			ENSP00000493592.1
VPS13A	ENST00000645632.1	c.2512+116A>G		intron_variant	Intron 24 of 68			ENSP00000496361.1

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

African (AFR) AF: 0.967 AC: 16098 AN: 16654

American (AMR) AF: 0.888 AC: 19500 AN: 21964

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 15181 AN: 17570

East Asian (EAS) AF: 0.876 AC: 27681 AN: 31598

South Asian (SAS) AF: 0.855 AC: 44476 AN: 52026

European-Finnish (FIN) AF: 0.733 AC: 23696 AN: 32328

Middle Eastern (MID) AF: 0.856 AC: 2153 AN: 2514

European-Non Finnish (NFE) AF: 0.778 AC: 373810 AN: 480306

Other (OTH) AF: 0.815 AC: 27606 AN: 33856

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

African (AFR) AF: 0.962 AC: 39975 AN: 41540

American (AMR) AF: 0.873 AC: 13345 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 3012 AN: 3472

East Asian (EAS) AF: 0.880 AC: 4546 AN: 5164

South Asian (SAS) AF: 0.860 AC: 4149 AN: 4824

European-Finnish (FIN) AF: 0.727 AC: 7671 AN: 10556

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52878 AN: 67990

Other (OTH) AF: 0.834 AC: 1759 AN: 2110

Alfa AF: 0.803 Hom.: 17452

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

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Chorea-acanthocytosis Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
DANN	Benign	0.55
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2050831; hg19: chr9-79888396;