Variant 2-86505929-T-C 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_016079.4(CHMP3):c.544A>G(p.Ser182Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000028 in 1,426,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

CHMP3
NM_016079.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.06

Variant links:

Genes affected

CHMP3 (HGNC:29865): (charged multivesicular body protein 3) This gene encodes a protein that sorts transmembrane proteins into lysosomes/vacuoles via the multivesicular body (MVB) pathway. This protein, along with other soluble coiled-coil containing proteins, forms part of the ESCRT-III protein complex that binds to the endosomal membrane and recruits additional cofactors for protein sorting into the MVB. This protein may also co-immunoprecipitate with a member of the IFG-binding protein superfamily. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the upstream ring finger protein 103 (RNF103) gene. [provided by RefSeq, Nov 2010]

CHMP3 links:

RNF103-CHMP3 (HGNC:):

RNF103-CHMP3 links:

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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=0.2595588).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHMP3	NM_016079.4 linkuse as main transcript	c.544A>G	p.Ser182Gly	missense_variant	6/6	ENST00000263856.9	NP_057163.1
RNF103-CHMP3	NM_001198954.1 linkuse as main transcript	c.631A>G	p.Ser211Gly	missense_variant	8/8		NP_001185883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHMP3	ENST00000263856.9 linkuse as main transcript	c.544A>G	p.Ser182Gly	missense_variant	6/6	1	NM_016079.4	ENSP00000263856	P1	Q9Y3E7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000439

AC:

AN:

227808

Hom.:

AF XY:

0.00000807

AC XY:

AN XY:

123902

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:

0.00000957

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000280

AC:

AN:

1426514

Hom.:

Cov.:

AF XY:

0.00000423

AC XY:

AN XY:

709090

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000366

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 17, 2023

The c.544A>G (p.S182G) alteration is located in exon 6 (coding exon 6) of the CHMP3 gene. This alteration results from a A to G substitution at nucleotide position 544, causing the serine (S) at amino acid position 182 to be replaced by a glycine (G). 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

0.067

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.28

T;.;.;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.79

T;T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.26

T;T;T;T

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.9

L;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PROVEAN

Benign

-1.6

N;N;N;.

REVEL

Benign

0.23

Sift

Benign

0.28

T;T;T;.

Sift4G

Benign

0.30

T;T;T;T

Polyphen

0.24

B;P;.;.

Vest4

0.17

MutPred

0.35

Loss of phosphorylation at S182 (P = 0.0343);.;.;.;

MVP

0.83

MPC

0.18

ClinPred

0.46

GERP RS

6.0

Varity_R

0.26

gMVP

0.46

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