rs139753431

Variant names:

• chr9-77344179-T-C
• rs139753431
• NM_033305.3:c.7053T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-77344179-T-C
• chr9-77344179-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_033305.3(VPS13A):​c.7053T>C​(p.Ala2351Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,609,510 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00062 (14 hom.)
• Consequence: VPS13A NM_033305.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.639
• Publications: 0 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=-0.52).
• BP6: Variant 9-77344179-T-C is Benign according to our data. Variant chr9-77344179-T-C is described in ClinVar as Benign. ClinVar VariationId is 448870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.639 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00575 (876/152248) while in subpopulation AFR AF = 0.0203 (845/41558). AF 95% confidence interval is 0.0192. There are 12 homozygotes in GnomAd4. There are 408 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13A	NM_033305.3	MANE Select	c.7053T>C	p.Ala2351Ala	synonymous	Exon 51 of 72	NP_150648.2
	VPS13A	NM_001018037.2		c.6936T>C	p.Ala2312Ala	synonymous	Exon 50 of 71	NP_001018047.1
	VPS13A	NM_015186.4		c.7053T>C	p.Ala2351Ala	synonymous	Exon 51 of 69	NP_056001.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13A	ENST00000360280.8	TSL:1 MANE Select	c.7053T>C	p.Ala2351Ala	synonymous	Exon 51 of 72	ENSP00000353422.3
	VPS13A	ENST00000376636.7	TSL:1	c.6936T>C	p.Ala2312Ala	synonymous	Exon 50 of 71	ENSP00000365823.3
	VPS13A	ENST00000643348.1		c.7053T>C	p.Ala2351Ala	synonymous	Exon 51 of 69	ENSP00000493592.1

Frequencies

GnomAD3 genomes AF: 0.00574 AC: 873 AN: 152130 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00156 AC: 393 AN: 251326 AF XY: 0.00110

Gnomad AFR exome AF: 0.0219

Gnomad AMR exome AF: 0.000781

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000620 AC: 904 AN: 1457262 Hom.: 14 Cov.: 30 AF XY: 0.000567 AC XY: 411 AN XY: 725260

African (AFR) AF: 0.0228 AC: 759 AN: 33352

American (AMR) AF: 0.000917 AC: 41 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39536

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.000697 AC: 4 AN: 5742

European-Non Finnish (NFE) AF: 0.00000451 AC: 5 AN: 1108060

Other (OTH) AF: 0.00139 AC: 84 AN: 60228

GnomAD4 genome AF: 0.00575 AC: 876 AN: 152248 Hom.: 12 Cov.: 32 AF XY: 0.00548 AC XY: 408 AN XY: 74450

African (AFR) AF: 0.0203 AC: 845 AN: 41558

American (AMR) AF: 0.00137 AC: 21 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68012

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00188 Hom.: 2

Bravo AF: 0.00692

Asia WGS AF: 0.000578 AC: 2 AN: 3472

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	Chorea-acanthocytosis (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.9
DANN	Benign	0.58
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism

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: rs139753431; hg19: chr9-79959095;