chr9-77320744-A-G

Variant names:

• chr9-77320744-A-G
• rs12380218
• NM_033305.3:c.5416-425A>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.5416-425A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 151,982 control chromosomes in the GnomAD database, including 3,722 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 0.20 (3722 hom., cov: 32)
• Consequence: VPS13A NM_033305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13A	NM_033305.3	c.5416-425A>G		intron_variant	Intron 42 of 71	ENST00000360280.8	NP_150648.2
VPS13A	NM_001018037.2	c.5299-425A>G		intron_variant	Intron 41 of 70		NP_001018047.1
VPS13A	NM_015186.4	c.5416-425A>G		intron_variant	Intron 42 of 68		NP_056001.1
VPS13A	NM_001018038.3	c.5416-425A>G		intron_variant	Intron 42 of 68		NP_001018048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13A	ENST00000360280.8	c.5416-425A>G		intron_variant	Intron 42 of 71	1	NM_033305.3	ENSP00000353422.3

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29668 AN: 151864 Hom.: 3719 Cov.: 32

Gnomad AFR AF: 0.0498

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.195 AC: 29674 AN: 151982 Hom.: 3722 Cov.: 32 AF XY: 0.202 AC XY: 15018 AN XY: 74246

African (AFR) AF: 0.0497 AC: 2066 AN: 41554

American (AMR) AF: 0.335 AC: 5107 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 761 AN: 3464

East Asian (EAS) AF: 0.379 AC: 1959 AN: 5168

South Asian (SAS) AF: 0.295 AC: 1421 AN: 4814

European-Finnish (FIN) AF: 0.261 AC: 2751 AN: 10554

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14831 AN: 67882

Other (OTH) AF: 0.213 AC: 449 AN: 2108

Alfa AF: 0.198 Hom.: 1398

Bravo AF: 0.196

Asia WGS AF: 0.322 AC: 1116 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.2
DANN	Benign	0.82
PhyloP100		-0.047
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: rs12380218; hg19: chr9-79935660;