dbSNP rs7086: VPS39:c.*1844C>G (chr15-42158910-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015289.5(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
NM_015289.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0860

Publications

13 publications found

Variant links:

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]

VPS39 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015289.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS39	NM_015289.5	MANE Select	c.*1844C>G		3_prime_UTR	Exon 25 of 25	NP_056104.2	Q96JC1-2
	VPS39	NM_001301138.3		c.*1844C>G		3_prime_UTR	Exon 26 of 26	NP_001288067.1	Q96JC1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VPS39	ENST00000318006.10	TSL:1 MANE Select	c.*1844C>G	3_prime_UTR	Exon 25 of 25	ENSP00000326534.5	Q96JC1-2
VPS39	ENST00000961232.1		c.*1844C>G	3_prime_UTR	Exon 25 of 25	ENSP00000631291.1
VPS39	ENST00000928544.1		c.*1844C>G	3_prime_UTR	Exon 25 of 25	ENSP00000598603.1

Frequencies

GnomAD3 genomes

AF:

0.365

AC:

55527

AN:

152034

Hom.:

17197

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.154

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.143

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.366

AC:

55665

AN:

152152

Hom.:

17266

Cov.:

AF XY:

0.364

AC XY:

27096

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.835

AC:

34626

AN:

41484

American (AMR)

AF:

0.408

AC:

6234

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

761

AN:

3472

East Asian (EAS)

AF:

0.204

AC:

1053

AN:

5172

South Asian (SAS)

AF:

0.320

AC:

1540

AN:

4820

European-Finnish (FIN)

AF:

0.129

AC:

1367

AN:

10590

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.137

AC:

9315

AN:

68000

Other (OTH)

AF:

0.326

AC:

689

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1095

2189

3284

4378

5473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.0

(source)

DANN

Benign

0.70

PhyloP100

-0.086

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over