Variant 8-23246786-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_152272.5(CHMP7):c.91A>C(p.Met31Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000049 in 1,429,546 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 (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

CHMP7
NM_152272.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.15

Variant links:

Genes affected

CHMP7 (HGNC:28439): (charged multivesicular body protein 7) Involved in several processes, including late endosome to vacuole transport; midbody abscission; and mitotic nuclear division. Located in cytosol; nuclear envelope; and nucleoplasm. Part of ESCRT III complex. Colocalizes with chromatin. [provided by Alliance of Genome Resources, Apr 2022]

CHMP7 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.36126378).

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHMP7	NM_152272.5 linkuse as main transcript	c.91A>C	p.Met31Leu	missense_variant	2/11	ENST00000397677.6	NP_689485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHMP7	ENST00000397677.6 linkuse as main transcript	c.91A>C	p.Met31Leu	missense_variant	2/11	1	NM_152272.5	ENSP00000380794	P1	Q8WUX9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000503

AC:

AN:

198668

Hom.:

AF XY:

0.00000933

AC XY:

AN XY:

107174

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000344

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000490

AC:

AN:

1429546

Hom.:

Cov.:

AF XY:

0.00000424

AC XY:

AN XY:

708342

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:

0.00000638

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000828

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

Oct 05, 2022

The c.91A>C (p.M31L) alteration is located in exon 2 (coding exon 1) of the CHMP7 gene. This alteration results from a A to C substitution at nucleotide position 91, causing the methionine (M) at amino acid position 31 to be replaced by a leucine (L). 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

Pathogenic

0.69

BayesDel_addAF

Uncertain

0.017

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Benign

0.89

DEOGEN2

Benign

0.10

T;T;T

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.65

.;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.1

M;M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.037

D;D;T

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.98

D;D;.

Vest4

0.49

MutPred

0.60

Loss of catalytic residue at M31 (P = 0.0022);Loss of catalytic residue at M31 (P = 0.0022);Loss of catalytic residue at M31 (P = 0.0022);

MVP

0.57

MPC

0.63

ClinPred

0.78

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.72

gMVP

0.85

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