rs2620381

Positions:

• chr15-42199650-A-C

Variant summary

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

The NM_015289.5(VPS39):​c.139+246T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 507,106 control chromosomes in the GnomAD database, including 840 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 0.049 (438 hom., cov: 31)
  • Exomes 𝑓: 0.019 (402 hom.)
• Consequence: VPS39 NM_015289.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215

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]

MIR627 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS39	NM_015289.5	c.139+246T>G		intron_variant		ENST00000318006.10	NP_056104.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS39	ENST00000318006.10	c.139+246T>G		intron_variant		1	NM_015289.5	ENSP00000326534.5
VPS39	ENST00000348544.4	c.139+246T>G		intron_variant		1		ENSP00000335193.5
MIR627	ENST00000384979.1	n.17T>G		non_coding_transcript_exon_variant	1/1	6
VPS39	ENST00000568357.1	n.293+246T>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0489 AC: 7406 AN: 151424 Hom.: 437 Cov.: 31

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0810

Gnomad SAS AF: 0.0534

Gnomad FIN AF: 0.00123

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00140

Gnomad OTH AF: 0.0404

GnomAD3 exomes AF: 0.0439 AC: 2546 AN: 57944 Hom.: 202 AF XY: 0.0396 AC XY: 1215 AN XY: 30668

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.177

Gnomad ASJ exome AF: 0.00156

Gnomad EAS exome AF: 0.0930

Gnomad SAS exome AF: 0.0469

Gnomad FIN exome AF: 0.00195

Gnomad NFE exome AF: 0.00134

Gnomad OTH exome AF: 0.0262

GnomAD4 exome AF: 0.0194 AC: 6903 AN: 355566 Hom.: 402 Cov.: 4 AF XY: 0.0196 AC XY: 3885 AN XY: 197986

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.00122

Gnomad4 EAS exome AF: 0.0885

Gnomad4 SAS exome AF: 0.0395

Gnomad4 FIN exome AF: 0.00134

Gnomad4 NFE exome AF: 0.00156

Gnomad4 OTH exome AF: 0.0213

GnomAD4 genome AF: 0.0490 AC: 7430 AN: 151540 Hom.: 438 Cov.: 31 AF XY: 0.0496 AC XY: 3672 AN XY: 74082

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.0810

Gnomad4 SAS AF: 0.0537

Gnomad4 FIN AF: 0.00123

Gnomad4 NFE AF: 0.00140

Gnomad4 OTH AF: 0.0400

Alfa AF: 0.0209 Hom.: 45

Bravo AF: 0.0620

Asia WGS AF: 0.0700 AC: 241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.74

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: rs2620381; hg19: chr15-42491848;