rs7086

Positions:

• chr15-42158910-G-C
• chr15-42158910-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000318006.10(VPS39):​c.*1844C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,192 control chromosomes in the GnomAD database, including 17,266 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 0.37 (17266 hom., cov: 32)
  • Exomes 𝑓: 0.15 (0 hom.)
• Consequence: VPS39 ENST00000318006.10 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860

Genes affected

VPS39 (HGNC:20593): (VPS39 subunit of HOPS complex) This gene encodes a protein that may promote clustering and fusion of late endosomes and lysosomes. The protein may also act as an adaptor protein that modulates the transforming growth factor-beta response by coupling the transforming growth factor-beta receptor complex to the Smad pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS39	NM_015289.5	c.*1844C>G		3_prime_UTR_variant	25/25	ENST00000318006.10	NP_056104.2
VPS39	NM_001301138.3	c.*1844C>G		3_prime_UTR_variant	26/26		NP_001288067.1
VPS39	XM_011521403.3	c.*1851C>G		3_prime_UTR_variant	26/26		XP_011519705.1
VPS39	XM_011521404.3	c.*1851C>G		3_prime_UTR_variant	25/25		XP_011519706.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS39	ENST00000318006.10	c.*1844C>G		3_prime_UTR_variant	25/25	1	NM_015289.5	ENSP00000326534	P4
VPS39	ENST00000562258.5	n.3966C>G		non_coding_transcript_exon_variant	8/8	2
VPS39	ENST00000614932.1	n.2638C>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55527 AN: 152034 Hom.: 17197 Cov.: 32

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.329

GnomAD4 exome AF: 0.150 AC: 6 AN: 40 Hom.: 0 Cov.: 0 AF XY: 0.154 AC XY: 4 AN XY: 26

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.366 AC: 55665 AN: 152152 Hom.: 17266 Cov.: 32 AF XY: 0.364 AC XY: 27096 AN XY: 74396

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.326

Alfa AF: 0.0777 Hom.: 124

Bravo AF: 0.406

Asia WGS AF: 0.294 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7086; hg19: chr15-42451108;