chr9-77369316-T-C

Variant names:

• chr9-77369316-T-C
• rs17340192
• NM_033305.3:c.8571T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033305.3(VPS13A):​c.8571T>C​(p.Tyr2857Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.081 in 1,610,632 control chromosomes in the GnomAD database, including 6,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (378 hom., cov: 33)
  • Exomes 𝑓: 0.083 (5633 hom.)
• Consequence: VPS13A NM_033305.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.30
• Publications: 8 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 9-77369316-T-C is Benign according to our data. Variant chr9-77369316-T-C is described in ClinVar as Benign. ClinVar VariationId is 367423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033305.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13A	NM_033305.3	MANE Select	c.8571T>C	p.Tyr2857Tyr	synonymous	Exon 63 of 72	NP_150648.2	Q96RL7-1
	VPS13A	NM_001018037.2		c.8454T>C	p.Tyr2818Tyr	synonymous	Exon 62 of 71	NP_001018047.1	Q96RL7-3
	VPS13A	NM_015186.4		c.8571T>C	p.Tyr2857Tyr	synonymous	Exon 63 of 69	NP_056001.1	Q96RL7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13A	ENST00000360280.8	TSL:1 MANE Select	c.8571T>C	p.Tyr2857Tyr	synonymous	Exon 63 of 72	ENSP00000353422.3	Q96RL7-1
	VPS13A	ENST00000376636.7	TSL:1	c.8454T>C	p.Tyr2818Tyr	synonymous	Exon 62 of 71	ENSP00000365823.3	Q96RL7-3
	VPS13A	ENST00000643348.1		c.8571T>C	p.Tyr2857Tyr	synonymous	Exon 63 of 69	ENSP00000493592.1	Q96RL7-2

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9127 AN: 152178 Hom.: 377 Cov.: 33

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0473

Gnomad ASJ AF: 0.0579

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0567

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0854

Gnomad OTH AF: 0.0578

GnomAD2 exomes AF: 0.0721 AC: 18126 AN: 251378 AF XY: 0.0780

Gnomad AFR exome AF: 0.0252

Gnomad AMR exome AF: 0.0304

Gnomad ASJ exome AF: 0.0685

Gnomad EAS exome AF: 0.000544

Gnomad FIN exome AF: 0.0624

Gnomad NFE exome AF: 0.0908

Gnomad OTH exome AF: 0.0752

GnomAD4 exome AF: 0.0832 AC: 121299 AN: 1458336 Hom.: 5633 Cov.: 30 AF XY: 0.0849 AC XY: 61639 AN XY: 725708

African (AFR) AF: 0.0207 AC: 692 AN: 33432

American (AMR) AF: 0.0324 AC: 1451 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0693 AC: 1809 AN: 26100

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39608

South Asian (SAS) AF: 0.126 AC: 10874 AN: 86182

European-Finnish (FIN) AF: 0.0647 AC: 3458 AN: 53412

Middle Eastern (MID) AF: 0.108 AC: 624 AN: 5764

European-Non Finnish (NFE) AF: 0.0883 AC: 97921 AN: 1108838

Other (OTH) AF: 0.0740 AC: 4461 AN: 60280

GnomAD4 genome AF: 0.0599 AC: 9124 AN: 152296 Hom.: 378 Cov.: 33 AF XY: 0.0589 AC XY: 4387 AN XY: 74466

African (AFR) AF: 0.0242 AC: 1004 AN: 41570

American (AMR) AF: 0.0471 AC: 721 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0579 AC: 201 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5188

South Asian (SAS) AF: 0.121 AC: 583 AN: 4822

European-Finnish (FIN) AF: 0.0567 AC: 602 AN: 10608

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0855 AC: 5813 AN: 68022

Other (OTH) AF: 0.0568 AC: 120 AN: 2114

Alfa AF: 0.0740 Hom.: 398

Bravo AF: 0.0566

Asia WGS AF: 0.0490 AC: 171 AN: 3478

EpiCase AF: 0.0845

EpiControl AF: 0.0869

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	3	Chorea-acanthocytosis (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	4.4
DANN	Benign	0.59
PhyloP100		1.3
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: rs17340192; hg19: chr9-79984232; COSMIC: COSV62429716;