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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
VPS39	NM_015289.5 link	c.*1844C>G	3_prime_UTR_variant	Exon 25 of 25	ENST00000318006.10	NP_056104.2	Q96JC1-2A0A024R9L9
VPS39	NM_001301138.3 link	c.*1844C>G	3_prime_UTR_variant	Exon 26 of 26		NP_001288067.1	Q96JC1-1
VPS39	XM_011521403.3 link	c.*1851C>G	3_prime_UTR_variant	Exon 26 of 26		XP_011519705.1
VPS39	XM_011521404.3 link	c.*1851C>G	3_prime_UTR_variant	Exon 25 of 25		XP_011519706.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
VPS39	ENST00000318006.10 link	c.*1844C>G	3_prime_UTR_variant	Exon 25 of 25	1	NM_015289.5	ENSP00000326534.5	Q96JC1-2
VPS39	ENST00000562258.5 link	n.3966C>G	non_coding_transcript_exon_variant	Exon 8 of 8	2
VPS39	ENST00000614932.1 link	n.2638C>G	non_coding_transcript_exon_variant	Exon 1 of 1	6

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over