rs879039152

Variant names:

• chr16-46660187-TTGTG-T
• rs879039152
• NM_018206.6:c.*281_*284delCACA

Your query was ambiguous. Multiple possible variants found:

• chr16-46660187-TTGTG-T
• chr16-46660187-TTGTG-TTG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_018206.6(VPS35):​c.*281_*284delCACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00047 in 53,214 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: 𝑓 0.000048 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00047 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VPS35 NM_018206.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.433

Genes affected

VPS35 (HGNC:13487): (VPS35 retromer complex component) This gene belongs to a group of vacuolar protein sorting (VPS) genes. The encoded protein is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. The close structural similarity between the yeast and human proteins that make up this complex suggests a similarity in function. Expression studies in yeast and mammalian cells indicate that this protein interacts directly with VPS35, which serves as the core of the retromer complex. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS35	NM_018206.6	c.*281_*284delCACA		3_prime_UTR_variant	Exon 17 of 17	ENST00000299138.12	NP_060676.2
VPS35	XM_011523227.4	c.*281_*284delCACA		3_prime_UTR_variant	Exon 17 of 17		XP_011521529.1
VPS35	XM_005256045.4	c.*281_*284delCACA		3_prime_UTR_variant	Exon 15 of 15		XP_005256102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VPS35	ENST00000299138	c.*281_*284delCACA		3_prime_UTR_variant	Exon 17 of 17	1	NM_018206.6	ENSP00000299138.7

Frequencies

GnomAD3 genomes AF: 0.0000479 AC: 4 AN: 83500 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000997

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000470 AC: 25 AN: 53214 Hom.: 0 AF XY: 0.000599 AC XY: 16 AN XY: 26712

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00131

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000837

Gnomad4 SAS exome AF: 0.00719

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000143

Gnomad4 OTH exome AF: 0.000551

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000479 AC: 4 AN: 83500 Hom.: 0 Cov.: 0 AF XY: 0.0000500 AC XY: 2 AN XY: 39988

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000997

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000185 Hom.: 0

Asia WGS AF: 0.00178 AC: 6 AN: 3378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs879039152; hg19: chr16-46694099;