rs35390554

Variant names:

• chr12-122232578-ATTTTT-A
• NM_022916.6:c.1610-156_1610-152delAAAAA

Your query was ambiguous. Multiple possible variants found:

• chr12-122232578-ATTTTT-A
• chr12-122232578-ATTTTT-ATTT
• chr12-122232578-ATTTTT-ATTTT
• chr12-122232578-ATTTTT-ATTTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_022916.6(VPS33A):​c.1610-156_1610-152delAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000113 in 886,844 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: VPS33A NM_022916.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16

Genes affected

VPS33A (HGNC:18179): (VPS33A core subunit of CORVET and HOPS complexes) This gene encodes a tethering protein and a core subunit of the homotypic fusion and protein sorting (HOPS) complex. The HOPS complex and a second endosomal tethering complex called the class C core vacuole/endosome tethering (CORVET) complex, perform diverse functions in endocytosis including membrane tethering, RabGTPase interaction, activation and proofreading of synaptic-soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) assembly to drive membrane fusion, and endosome-to-cytoskeleton attachment. The HOPS complex controls endosome maturation as well as endosome traffic to the lysosome. This complex is essential for vacuolar fusion and is required for adaptor protein complex 3-dependent transport from the golgi to the vacuole. The encoded protein belongs to the Sec1/Munc18 (SM) family of SNARE-mediated membrane fusion regulators. Naturally occurring mutations in this gene are associated with a novel mucopolysaccharidosis-like disease. [provided by RefSeq, Apr 2017]

ENSG00000256861 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS33A	NM_022916.6	c.1610-156_1610-152delAAAAA		intron_variant	Intron 12 of 12	ENST00000267199.9	NP_075067.2
VPS33A	NM_001351018.2	c.1577-156_1577-152delAAAAA		intron_variant	Intron 12 of 12		NP_001337947.1
VPS33A	NM_001351019.2	c.1562-156_1562-152delAAAAA		intron_variant	Intron 12 of 12		NP_001337948.1
VPS33A	NM_001351020.2	c.1289-156_1289-152delAAAAA		intron_variant	Intron 10 of 10		NP_001337949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS33A	ENST00000267199.9	c.1610-156_1610-152delAAAAA		intron_variant	Intron 12 of 12	1	NM_022916.6	ENSP00000267199.3
ENSG00000256861	ENST00000535844.1	n.1493-156_1493-152delAAAAA		intron_variant	Intron 11 of 15	2		ENSP00000454454.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000113 AC: 1 AN: 886844 Hom.: 0 AF XY: 0.00000226 AC XY: 1 AN XY: 441802

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000148

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-122717125;