chr1-12236175-C-A

Variant names:

• chr1-12236175-C-A
• rs235256
• NM_015378.4:c.97+1812C>A

Variant summary

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

The NM_015378.4(VPS13D):​c.97+1812C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,972 control chromosomes in the GnomAD database, including 6,658 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 0.23 (6658 hom., cov: 32)
• Consequence: VPS13D NM_015378.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.960
• Publications: 5 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: Labcorp Genetics (formerly Invitae), Orphanet, Illumina, Ambry Genetics
• Leigh syndrome

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015378.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13D	NM_015378.4	MANE Select	c.97+1812C>A		intron	N/A	NP_056193.2	Q5THJ4-1
	VPS13D	NM_018156.4		c.97+1812C>A		intron	N/A	NP_060626.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS13D	ENST00000620676.6	TSL:1 MANE Select	c.97+1812C>A		intron	N/A	ENSP00000478104.1	Q5THJ4-1
	VPS13D	ENST00000613099.4	TSL:1	c.97+1812C>A		intron	N/A	ENSP00000482233.1	Q5THJ4-2

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34183 AN: 151854 Hom.: 6620 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0977

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0784

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.226 AC: 34275 AN: 151972 Hom.: 6658 Cov.: 32 AF XY: 0.226 AC XY: 16807 AN XY: 74282

African (AFR) AF: 0.525 AC: 21737 AN: 41420

American (AMR) AF: 0.251 AC: 3828 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 380 AN: 3470

East Asian (EAS) AF: 0.160 AC: 827 AN: 5160

South Asian (SAS) AF: 0.140 AC: 676 AN: 4814

European-Finnish (FIN) AF: 0.0977 AC: 1032 AN: 10560

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0784 AC: 5328 AN: 67982

Other (OTH) AF: 0.192 AC: 405 AN: 2110

Alfa AF: 0.116 Hom.: 3645

Bravo AF: 0.251

Asia WGS AF: 0.176 AC: 611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.0
DANN	Benign	0.52
PhyloP100		0.96
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: rs235256; hg19: chr1-12296232;