9-77276321-T-G

Variant names:

• chr9-77276321-T-G
• rs7030802
• NM_033305.3:c.2824+100T>G

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.2824+100T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,115,318 control chromosomes in the GnomAD database, including 24,935 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3523 hom., cov: 32)
  • Exomes 𝑓: 0.20 (21412 hom.)
• Consequence: VPS13A NM_033305.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.124
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 9-77276321-T-G is Benign according to our data. Variant chr9-77276321-T-G is described in ClinVar as Benign. ClinVar VariationId is 1228232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13A	NM_033305.3	c.2824+100T>G		intron_variant	Intron 26 of 71	ENST00000360280.8	NP_150648.2
VPS13A	NM_001018037.2	c.2824+100T>G		intron_variant	Intron 26 of 70		NP_001018047.1
VPS13A	NM_015186.4	c.2824+100T>G		intron_variant	Intron 26 of 68		NP_056001.1
VPS13A	NM_001018038.3	c.2824+100T>G		intron_variant	Intron 26 of 68		NP_001018048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13A	ENST00000360280.8	c.2824+100T>G		intron_variant	Intron 26 of 71	1	NM_033305.3	ENSP00000353422.3
VPS13A	ENST00000376636.7	c.2824+100T>G		intron_variant	Intron 26 of 70	1		ENSP00000365823.3
VPS13A	ENST00000643348.1	c.2824+100T>G		intron_variant	Intron 26 of 68			ENSP00000493592.1
VPS13A	ENST00000645632.1	c.2824+100T>G		intron_variant	Intron 26 of 68			ENSP00000496361.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31513 AN: 152032 Hom.: 3516 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0333

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.205 AC: 197086 AN: 963168 Hom.: 21412 AF XY: 0.205 AC XY: 98632 AN XY: 481392

African (AFR) AF: 0.263 AC: 5734 AN: 21810

American (AMR) AF: 0.111 AC: 2046 AN: 18464

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 3449 AN: 18610

East Asian (EAS) AF: 0.0291 AC: 935 AN: 32164

South Asian (SAS) AF: 0.227 AC: 11342 AN: 49910

European-Finnish (FIN) AF: 0.176 AC: 5696 AN: 32342

Middle Eastern (MID) AF: 0.233 AC: 702 AN: 3018

European-Non Finnish (NFE) AF: 0.213 AC: 158929 AN: 744504

Other (OTH) AF: 0.195 AC: 8253 AN: 42346

GnomAD4 genome AF: 0.207 AC: 31545 AN: 152150 Hom.: 3523 Cov.: 32 AF XY: 0.203 AC XY: 15114 AN XY: 74412

African (AFR) AF: 0.258 AC: 10726 AN: 41504

American (AMR) AF: 0.148 AC: 2267 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 647 AN: 3470

East Asian (EAS) AF: 0.0333 AC: 173 AN: 5188

South Asian (SAS) AF: 0.220 AC: 1063 AN: 4822

European-Finnish (FIN) AF: 0.168 AC: 1778 AN: 10586

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.211 AC: 14311 AN: 67966

Other (OTH) AF: 0.187 AC: 394 AN: 2106

Alfa AF: 0.193 Hom.: 1582

Bravo AF: 0.206

Asia WGS AF: 0.118 AC: 411 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.63
PhyloP100		0.12
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: rs7030802; hg19: chr9-79891237;