9-77334940-C-T

Position:

• chr9-77334940-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033305.3(VPS13A):​c.6096-2315C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,052 control chromosomes in the GnomAD database, including 2,836 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 0.17 (2836 hom., cov: 32)
• Consequence: VPS13A NM_033305.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS13A	NM_033305.3	c.6096-2315C>T		intron_variant		ENST00000360280.8	NP_150648.2
VPS13A	NM_001018037.2	c.5979-2315C>T		intron_variant			NP_001018047.1
VPS13A	NM_015186.4	c.6096-2315C>T		intron_variant			NP_056001.1
VPS13A	NM_001018038.3	c.6096-2315C>T		intron_variant			NP_001018048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13A	ENST00000360280.8	c.6096-2315C>T		intron_variant		1	NM_033305.3	ENSP00000353422.3

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26117 AN: 151936 Hom.: 2837 Cov.: 32

Gnomad AFR AF: 0.0538

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.286

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.190

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

GnomAD4 genome AF: 0.172 AC: 26113 AN: 152052 Hom.: 2836 Cov.: 32 AF XY: 0.179 AC XY: 13291 AN XY: 74312

Gnomad4 AFR AF: 0.0536

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.389

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.194

Alfa AF: 0.188 Hom.: 1398

Bravo AF: 0.171

Asia WGS AF: 0.315 AC: 1093 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.6
DANN	Benign	0.61

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: rs11145388; hg19: chr9-79949856;