Genetic Variant VPS13D:c.98-183G>A (chr1-12242330-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_015378.4(VPS13D):c.98-183G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0621 in 152,154 control chromosomes in the GnomAD database, including 482 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.062 ( 482 hom., cov: 32)

Consequence

VPS13D
NM_015378.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.45

Publications

1 publications found

Variant links:

Genes affected

VPS13D (HGNC:23595): (vacuolar protein sorting 13 homolog D) This gene encodes a protein belonging to the vacuolar-protein-sorting-13 gene family. In yeast, vacuolar-protein-sorting-13 proteins are involved in trafficking of membrane proteins between the trans-Golgi network and the prevacuolar compartment. While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode distinct isoforms. [provided by RefSeq, Jul 2008]

VPS13D Gene-Disease associations (from GenCC):

autosomal recessive cerebellar ataxia-saccadic intrusion syndrome
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
Leigh syndrome
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

VPS13D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-12242330-G-A is Benign according to our data. Variant chr1-12242330-G-A is described in ClinVar as Benign. ClinVar VariationId is 1243262.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13D	NM_015378.4 link	c.98-183G>A		intron_variant	Intron 2 of 69	ENST00000620676.6	NP_056193.2	Q5THJ4-1
VPS13D	NM_018156.4 link	c.98-183G>A		intron_variant	Intron 2 of 68		NP_060626.2	Q5THJ4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13D	ENST00000620676.6 link	c.98-183G>A		intron_variant	Intron 2 of 69	1	NM_015378.4	ENSP00000478104.1		Q5THJ4-1
VPS13D	ENST00000613099.4 link	c.98-183G>A		intron_variant	Intron 2 of 68	1		ENSP00000482233.1		Q5THJ4-2

Frequencies

GnomAD3 genomes

AF:

0.0619

AC:

9414

AN:

152036

Hom.:

476

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.0548

Gnomad EAS

AF:

0.0167

Gnomad SAS

AF:

0.0651

Gnomad FIN

AF:

0.0214

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0256

Gnomad OTH

AF:

0.0550

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

GnomAD4 genome

AF:

0.0621

AC:

9450

AN:

152154

Hom.:

482

Cov.:

AF XY:

0.0643

AC XY:

4780

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.112

AC:

4636

AN:

41484

American (AMR)

AF:

0.137

AC:

2097

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0548

AC:

190

AN:

3464

East Asian (EAS)

AF:

0.0168

AC:

AN:

5184

South Asian (SAS)

AF:

0.0653

AC:

315

AN:

4822

European-Finnish (FIN)

AF:

0.0214

AC:

226

AN:

10582

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0256

AC:

1740

AN:

68006

Other (OTH)

AF:

0.0572

AC:

121

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

434

868

1301

1735

2169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0537

Hom.:

Bravo

AF:

0.0722

Asia WGS

AF:

0.0560

AC:

194

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 16, 2021

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

-0.88

CADD

Benign

0.098

(source)

DANN

Benign

0.62

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over