9-77209086-C-T

Position:

• chr9-77209086-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_033305.3(VPS13A):​c.386-337C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,096 control chromosomes in the GnomAD database, including 3,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3307 hom., cov: 32)
• Consequence: VPS13A NM_033305.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.00

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-77209086-C-T is Benign according to our data. Variant chr9-77209086-C-T is described in ClinVar as [Benign]. Clinvar id is 1234354.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS13A	NM_033305.3	c.386-337C>T		intron_variant		ENST00000360280.8	NP_150648.2
VPS13A	NM_001018037.2	c.386-337C>T		intron_variant			NP_001018047.1
VPS13A	NM_015186.4	c.386-337C>T		intron_variant			NP_056001.1
VPS13A	NM_001018038.3	c.386-337C>T		intron_variant			NP_001018048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS13A	ENST00000360280.8	c.386-337C>T		intron_variant		1	NM_033305.3	ENSP00000353422.3
VPS13A	ENST00000376636.7	c.386-337C>T		intron_variant		1		ENSP00000365823.3
VPS13A	ENST00000643348.1	c.386-337C>T		intron_variant				ENSP00000493592.1
VPS13A	ENST00000645632.1	c.386-337C>T		intron_variant				ENSP00000496361.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29498 AN: 151978 Hom.: 3309 Cov.: 32

Gnomad AFR AF: 0.0982

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.194 AC: 29497 AN: 152096 Hom.: 3307 Cov.: 32 AF XY: 0.201 AC XY: 14943 AN XY: 74326

Gnomad4 AFR AF: 0.0979

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.215

Alfa AF: 0.200 Hom.: 5290

Bravo AF: 0.194

Asia WGS AF: 0.323 AC: 1122 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.38
DANN	Benign	0.34

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: rs10869910; hg19: chr9-79824002;