rs3737289

Variant names:

• chr9-77371141-A-G
• rs3737289
• NM_033305.3:c.9069A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-77371141-A-G
• chr9-77371141-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_033305.3(VPS13A):​c.9069A>G​(p.Gly3023Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,613,544 control chromosomes in the GnomAD database, including 156,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G3023G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.41 (12981 hom., cov: 32)
  • Exomes 𝑓: 0.44 (143795 hom.)
• Consequence: VPS13A NM_033305.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.349
• Publications: 22 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 9-77371141-A-G is Benign according to our data. Variant chr9-77371141-A-G is described in ClinVar as Benign. ClinVar VariationId is 367428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.349 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.508 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.9069A>G	p.Gly3023Gly	synonymous	Exon 67 of 72	NP_150648.2
	VPS13A	NM_001018037.2		c.8952A>G	p.Gly2984Gly	synonymous	Exon 66 of 71	NP_001018047.1
	VPS13A	NM_015186.4		c.9069A>G	p.Gly3023Gly	synonymous	Exon 67 of 69	NP_056001.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13A	ENST00000360280.8	TSL:1 MANE Select	c.9069A>G	p.Gly3023Gly	synonymous	Exon 67 of 72	ENSP00000353422.3
	VPS13A	ENST00000376636.7	TSL:1	c.8952A>G	p.Gly2984Gly	synonymous	Exon 66 of 71	ENSP00000365823.3
	VPS13A	ENST00000643348.1		c.9069A>G	p.Gly3023Gly	synonymous	Exon 67 of 69	ENSP00000493592.1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61972 AN: 151926 Hom.: 12970 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.398

GnomAD2 exomes AF: 0.454 AC: 113950 AN: 250736 AF XY: 0.456

Gnomad AFR exome AF: 0.314

Gnomad AMR exome AF: 0.576

Gnomad ASJ exome AF: 0.414

Gnomad EAS exome AF: 0.374

Gnomad FIN exome AF: 0.447

Gnomad NFE exome AF: 0.433

Gnomad OTH exome AF: 0.441

GnomAD4 exome AF: 0.441 AC: 643904 AN: 1461500 Hom.: 143795 Cov.: 55 AF XY: 0.443 AC XY: 321733 AN XY: 727056

African (AFR) AF: 0.315 AC: 10537 AN: 33466

American (AMR) AF: 0.558 AC: 24941 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 10788 AN: 26128

East Asian (EAS) AF: 0.339 AC: 13465 AN: 39682

South Asian (SAS) AF: 0.536 AC: 46228 AN: 86240

European-Finnish (FIN) AF: 0.449 AC: 23949 AN: 53380

Middle Eastern (MID) AF: 0.444 AC: 2563 AN: 5768

European-Non Finnish (NFE) AF: 0.437 AC: 485740 AN: 1111744

Other (OTH) AF: 0.425 AC: 25693 AN: 60390

GnomAD4 genome AF: 0.408 AC: 62012 AN: 152044 Hom.: 12981 Cov.: 32 AF XY: 0.411 AC XY: 30571 AN XY: 74308

African (AFR) AF: 0.319 AC: 13250 AN: 41476

American (AMR) AF: 0.490 AC: 7484 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1386 AN: 3470

East Asian (EAS) AF: 0.365 AC: 1886 AN: 5174

South Asian (SAS) AF: 0.525 AC: 2525 AN: 4806

European-Finnish (FIN) AF: 0.448 AC: 4723 AN: 10552

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29372 AN: 67974

Other (OTH) AF: 0.400 AC: 843 AN: 2108

Alfa AF: 0.418 Hom.: 40015

Bravo AF: 0.406

Asia WGS AF: 0.422 AC: 1467 AN: 3478

EpiCase AF: 0.434

EpiControl AF: 0.431

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Chorea-acanthocytosis (4)
-	-	4	not provided (4)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.2
DANN	Benign	0.69
PhyloP100		-0.35
Mutation Taster		=74/26	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: rs3737289; hg19: chr9-79986057; COSMIC: COSV62426716;