Variant 12-122867277-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000267202.7(VPS37B):c.697G>A(p.Val233Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000337 in 1,393,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

VPS37B
ENST00000267202.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.37

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05029267).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS37B	NM_024667.3 linkuse as main transcript	c.697G>A	p.Val233Met	missense_variant	4/4	ENST00000267202.7	NP_078943.1	Q9H9H4A0A024RBU0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VPS37B	ENST00000267202.7 linkuse as main transcript	c.697G>A	p.Val233Met	missense_variant	4/4	1	NM_024667.3	ENSP00000267202.2		Q9H9H4
VPS37B	ENST00000535765.5 linkuse as main transcript	c.691G>A	p.Val231Met	missense_variant	4/4	3		ENSP00000446075.1		F5H4M0

Frequencies

GnomAD3 genomes

AF:

0.00000719

AC:

AN:

139094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000238

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000487

AC:

AN:

205190

Hom.:

AF XY:

0.0000448

AC XY:

AN XY:

111656

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000582

Gnomad SAS exome

AF:

0.0000855

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000656

Gnomad OTH exome

AF:

0.000204

GnomAD4 exome

AF:

0.0000337

AC:

AN:

1393548

Hom.:

Cov.:

AF XY:

0.0000363

AC XY:

AN XY:

689426

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000803

Gnomad4 SAS exome

AF:

0.0000754

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000317

Gnomad4 OTH exome

AF:

0.0000705

GnomAD4 genome

Cov.:

Alfa

AF:

0.000121

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000579

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2022

The c.697G>A (p.V233M) alteration is located in exon 4 (coding exon 4) of the VPS37B gene. This alteration results from a G to A substitution at nucleotide position 697, causing the valine (V) at amino acid position 233 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.55

CADD

Benign

2.1

DANN

Benign

0.83

DEOGEN2

Benign

0.023

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.18

N;N

REVEL

Benign

0.077

Sift

Benign

0.088

T;T

Sift4G

Benign

0.16

T;.

Polyphen

0.0010

B;.

Vest4

0.038

MutPred

0.12

Loss of phosphorylation at Y235 (P = 0.0746);.;

MVP

0.36

MPC

0.29

ClinPred

0.025

GERP RS

-6.8

Varity_R

0.027

gMVP

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over