9-77254936-T-G

Variant names:

• chr9-77254936-T-G
• rs2022443
• NM_033305.3:c.2288+2584T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033305.3(VPS13A):​c.2288+2584T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,072 control chromosomes in the GnomAD database, including 4,168 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 0.22 (4168 hom., cov: 32)
• Consequence: VPS13A NM_033305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13A	NM_033305.3	c.2288+2584T>G		intron_variant	Intron 22 of 71	ENST00000360280.8	NP_150648.2
VPS13A	NM_001018037.2	c.2288+2584T>G		intron_variant	Intron 22 of 70		NP_001018047.1
VPS13A	NM_015186.4	c.2288+2584T>G		intron_variant	Intron 22 of 68		NP_056001.1
VPS13A	NM_001018038.3	c.2288+2584T>G		intron_variant	Intron 22 of 68		NP_001018048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13A	ENST00000360280.8	c.2288+2584T>G		intron_variant	Intron 22 of 71	1	NM_033305.3	ENSP00000353422.3
VPS13A	ENST00000376636.7	c.2288+2584T>G		intron_variant	Intron 22 of 70	1		ENSP00000365823.3
VPS13A	ENST00000643348.1	c.2288+2584T>G		intron_variant	Intron 22 of 68			ENSP00000493592.1
VPS13A	ENST00000645632.1	c.2288+2584T>G		intron_variant	Intron 22 of 68			ENSP00000496361.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33155 AN: 151954 Hom.: 4165 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.218 AC: 33170 AN: 152072 Hom.: 4168 Cov.: 32 AF XY: 0.225 AC XY: 16743 AN XY: 74362

African (AFR) AF: 0.112 AC: 4637 AN: 41528

American (AMR) AF: 0.349 AC: 5334 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 779 AN: 3472

East Asian (EAS) AF: 0.395 AC: 2036 AN: 5152

South Asian (SAS) AF: 0.312 AC: 1507 AN: 4826

European-Finnish (FIN) AF: 0.266 AC: 2813 AN: 10564

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15207 AN: 67958

Other (OTH) AF: 0.233 AC: 492 AN: 2110

Alfa AF: 0.190 Hom.: 1043

Bravo AF: 0.220

Asia WGS AF: 0.336 AC: 1166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.1
DANN	Benign	0.56
PhyloP100		0.082
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2022443; hg19: chr9-79869852;