Variant 12-122867414-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024667.3(VPS37B):c.560C>T(p.Ala187Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000761 in 1,446,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 25)

Exomes 𝑓: 0.000076 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

VPS37B
NM_024667.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.68

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09762323).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VPS37B	NM_024667.3 linkuse as main transcript	c.560C>T	p.Ala187Val	missense_variant	4/4	ENST00000267202.7	NP_078943.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
VPS37B	ENST00000267202.7 linkuse as main transcript	c.560C>T	p.Ala187Val	missense_variant	4/4	1	NM_024667.3	ENSP00000267202	P1
VPS37B	ENST00000535765.5 linkuse as main transcript	c.554C>T	p.Ala185Val	missense_variant	4/4	3		ENSP00000446075
VPS37B	ENST00000371248.3 linkuse as main transcript			downstream_gene_variant		3		ENSP00000360294

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149384

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000893

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000204

AC:

AN:

245238

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

133466

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000451

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000761

AC:

110

AN:

1446188

Hom.:

Cov.:

AF XY:

0.0000792

AC XY:

AN XY:

719912

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000905

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000402

AC:

AN:

149384

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

72804

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000893

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000907

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jun 02, 2023

The c.560C>T (p.A187V) alteration is located in exon 4 (coding exon 4) of the VPS37B gene. This alteration results from a C to T substitution at nucleotide position 560, causing the alanine (A) at amino acid position 187 to be replaced by a valine (V). 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

0.068

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.4

DANN

Benign

0.73

DEOGEN2

Benign

0.027

T;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.53

T;T

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.098

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.065

Sift

Benign

0.25

T;T

Sift4G

Benign

0.55

T;.

Polyphen

0.10

B;.

Vest4

0.080

MutPred

0.14

Loss of relative solvent accessibility (P = 0.0981);.;

MVP

0.21

MPC

0.29

ClinPred

0.10

GERP RS

4.4

Varity_R

0.030

gMVP

0.30

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