1-12242330-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.45

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
VPS13D	NM_015378.4	c.98-183G>A		intron_variant		ENST00000620676.6
VPS13D	NM_018156.4	c.98-183G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VPS13D	ENST00000620676.6	c.98-183G>A		intron_variant		1	NM_015378.4	P3
VPS13D	ENST00000613099.4	c.98-183G>A		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.0619 AC: 9414 AN: 152036 Hom.: 476 Cov.: 32

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.: 32 AF XY: 0.0643 AC XY: 4780 AN XY: 74376

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0548

Gnomad4 EAS AF: 0.0168

Gnomad4 SAS AF: 0.0653

Gnomad4 FIN AF: 0.0214

Gnomad4 NFE AF: 0.0256

Gnomad4 OTH AF: 0.0572

Alfa AF: 0.0516 Hom.: 31

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.098
Dann	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs35946916; hg19: chr1-12302387; COSMIC: COSV62534681; COSMIC: COSV62534681;