Genetic Variant VPS37B:p.Pro241Gln (chr12-122867252-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024667.3(VPS37B):c.722C>A(p.Pro241Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P241L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

VPS37B
NM_024667.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.52

Publications

3 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:

ENSG00000256152 (HGNC:):

ENSG00000256152 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.722C>A	p.Pro241Gln	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.722C>A	p.Pro241Gln	missense	Exon 4 of 4	ENSP00000267202.2	Q9H9H4
VPS37B	ENST00000535765.5	TSL:3	c.716C>A	p.Pro239Gln	missense	Exon 4 of 4	ENSP00000446075.1	F5H4M0
VPS37B	ENST00000852158.1		c.467C>A	p.Pro156Gln	missense	Exon 2 of 2	ENSP00000522217.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

200006

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1418624

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

702910

African (AFR)

AF:

0.00

AC:

AN:

32062

American (AMR)

AF:

0.00

AC:

AN:

37706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22670

East Asian (EAS)

AF:

0.00

AC:

AN:

39510

South Asian (SAS)

AF:

0.00

AC:

AN:

78788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5298

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093958

Other (OTH)

AF:

0.00

AC:

AN:

58586

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.42

MetaRNN

Uncertain

0.60

MetaSVM

Uncertain

-0.24

MutationAssessor

Uncertain

2.5

PhyloP100

4.5

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-4.1

REVEL

Uncertain

0.41

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.34

MutPred

0.35

Loss of catalytic residue at P241 (P = 0.0261)

MVP

0.17

MPC

0.90

ClinPred

0.99

GERP RS

4.5

Varity_R

0.60

gMVP

0.46

Mutation Taster

=61/39

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over