rs545755034

Variant names:

• chr16-46660126-C-A
• rs545755034
• NM_018206.6:c.*346G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-46660126-C-A
• chr16-46660126-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018206.6(VPS35):​c.*346G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000707 in 141,418 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000071 (0 hom., cov: 32)
• Consequence: VPS35 NM_018206.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.368

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VPS35	NM_018206.6	c.*346G>T		3_prime_UTR_variant	Exon 17 of 17	ENST00000299138.12	NP_060676.2
VPS35	XM_011523227.4	c.*346G>T		3_prime_UTR_variant	Exon 17 of 17		XP_011521529.1
VPS35	XM_005256045.4	c.*346G>T		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.*346G>T		3_prime_UTR_variant	Exon 17 of 17	1	NM_018206.6	ENSP00000299138.7

Frequencies

GnomAD3 genomes AF: 0.00000707 AC: 1 AN: 141418 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000262

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.00000707 AC: 1 AN: 141418 Hom.: 0 Cov.: 32 AF XY: 0.0000147 AC XY: 1 AN XY: 68096

Gnomad4 AFR AF: 0.0000262

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: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.9
DANN	Benign	0.71

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: rs545755034; hg19: chr16-46694038;