1-12366666-C-T

Variant names:

• chr1-12366666-C-T
• rs10864553
• NM_015378.4:c.10449-1802C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015378.4(VPS13D):​c.10449-1802C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,132 control chromosomes in the GnomAD database, including 2,259 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (2259 hom., cov: 32)
• Consequence: VPS13D NM_015378.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.802
• Publications: 3 publications found

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

ENSG00000295309 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS13D	NM_015378.4	c.10449-1802C>T		intron_variant	Intron 52 of 69	ENST00000620676.6	NP_056193.2
VPS13D	NM_018156.4	c.10374-1802C>T		intron_variant	Intron 51 of 68		NP_060626.2
LOC124903845	XR_007065468.1	n.120+2084G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS13D	ENST00000620676.6	c.10449-1802C>T		intron_variant	Intron 52 of 69	1	NM_015378.4	ENSP00000478104.1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18955 AN: 152014 Hom.: 2249 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0438

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0834

Gnomad FIN AF: 0.0475

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0360

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.125 AC: 18995 AN: 152132 Hom.: 2259 Cov.: 32 AF XY: 0.125 AC XY: 9301 AN XY: 74372

African (AFR) AF: 0.312 AC: 12935 AN: 41472

American (AMR) AF: 0.103 AC: 1572 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0438 AC: 152 AN: 3470

East Asian (EAS) AF: 0.143 AC: 741 AN: 5172

South Asian (SAS) AF: 0.0824 AC: 397 AN: 4818

European-Finnish (FIN) AF: 0.0475 AC: 503 AN: 10596

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0360 AC: 2450 AN: 68016

Other (OTH) AF: 0.104 AC: 220 AN: 2108

Alfa AF: 0.0975 Hom.: 338

Bravo AF: 0.137

Asia WGS AF: 0.113 AC: 392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.49
DANN	Benign	0.79
PhyloP100		-0.80
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: rs10864553; hg19: chr1-12426721;