dbSNP rs761157980: VPS37B:p.Pro208Leu (chr12-122867351-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_024667.3(VPS37B):c.623C>T(p.Pro208Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000564 in 1,596,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P208H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 23)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

VPS37B
NM_024667.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.20

Publications

0 publications found

Variant links:

Genes affected

VPS37B (HGNC:25754): (VPS37B subunit of ESCRT-I) Enables calcium-dependent protein binding activity. Involved in positive regulation of viral budding via host ESCRT complex. Located in endosome membrane; midbody; and plasma membrane. Part of ESCRT I complex. [provided by Alliance of Genome Resources, Apr 2022]

VPS37B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39988726).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024667.3. 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
	VPS37B	NM_024667.3	MANE Select	c.623C>T	p.Pro208Leu	missense	Exon 4 of 4	NP_078943.1	Q9H9H4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VPS37B	ENST00000267202.7	TSL:1 MANE Select	c.623C>T	p.Pro208Leu	missense	Exon 4 of 4	ENSP00000267202.2	Q9H9H4
VPS37B	ENST00000535765.5	TSL:3	c.617C>T	p.Pro206Leu	missense	Exon 4 of 4	ENSP00000446075.1	F5H4M0
VPS37B	ENST00000852158.1		c.368C>T	p.Pro123Leu	missense	Exon 2 of 2	ENSP00000522217.1

Frequencies

GnomAD3 genomes

AF:

0.0000333

AC:

AN:

150178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000490

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

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

GnomAD2 exomes

AF:

0.00

AC:

AN:

228460

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1446290

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718962

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33176

American (AMR)

AF:

0.0000456

AC:

AN:

43886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25672

East Asian (EAS)

AF:

0.00

AC:

AN:

39266

South Asian (SAS)

AF:

0.00

AC:

AN:

85754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49166

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4808

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1104948

Other (OTH)

AF:

0.0000168

AC:

AN:

59614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.588

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:

0.0000333

AC:

AN:

150178

Hom.:

Cov.:

AF XY:

0.0000546

AC XY:

AN XY:

73216

show subpopulations

African (AFR)

AF:

0.0000490

AC:

AN:

40790

American (AMR)

AF:

0.000198

AC:

AN:

15150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5056

South Asian (SAS)

AF:

0.00

AC:

AN:

4680

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67342

Other (OTH)

AF:

0.00

AC:

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.565

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Uncertain

0.024

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Benign

0.14

Eigen_PC

Benign

0.097

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.78

M_CAP

Benign

0.065

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.5

PhyloP100

5.2

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.23

Sift

Uncertain

0.018

Sift4G

Uncertain

0.023

Polyphen

0.78

Vest4

0.40

MutPred

0.34

Loss of glycosylation at P208 (P = 0.0112)

MVP

0.19

MPC

0.53

ClinPred

0.98

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.49

Mutation Taster

=77/23

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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