rs7864334

Positions:

• chr9-77289640-T-C
• chr9-77289640-T-G

Variant summary

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

The ENST00000360280.8(VPS13A):​c.3340-3701T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 152,028 control chromosomes in the GnomAD database, including 28,868 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 0.61 (28868 hom., cov: 32)
• Consequence: VPS13A ENST00000360280.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS13A	NM_033305.3	c.3340-3701T>C		intron_variant		ENST00000360280.8	NP_150648.2
VPS13A	NM_001018037.2	c.3223-3701T>C		intron_variant			NP_001018047.1
VPS13A	NM_001018038.3	c.3340-3701T>C		intron_variant			NP_001018048.1
VPS13A	NM_015186.4	c.3340-3701T>C		intron_variant			NP_056001.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13A	ENST00000360280.8	c.3340-3701T>C		intron_variant		1	NM_033305.3	ENSP00000353422	P4

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92395 AN: 151910 Hom.: 28815 Cov.: 32

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.609 AC: 92512 AN: 152028 Hom.: 28868 Cov.: 32 AF XY: 0.609 AC XY: 45232 AN XY: 74278

Gnomad4 AFR AF: 0.742

Gnomad4 AMR AF: 0.642

Gnomad4 ASJ AF: 0.578

Gnomad4 EAS AF: 0.686

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.494

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.603

Alfa AF: 0.560 Hom.: 11019

Bravo AF: 0.624

Asia WGS AF: 0.651 AC: 2261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.2
DANN	Benign	0.71

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: rs7864334; hg19: chr9-79904556;