dbSNP rs1242418468: CHMP7:p.Ser284Cys (chr8-23258340-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152272.5(CHMP7):c.851C>G(p.Ser284Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. S284F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Consequence

CHMP7
NM_152272.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.11

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13832045).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152272.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHMP7	NM_152272.5	MANE Select	c.851C>G	p.Ser284Cys	missense	Exon 7 of 11	NP_689485.1	Q8WUX9-1
CHMP7	NM_001363183.2		c.851C>G	p.Ser284Cys	missense	Exon 6 of 9	NP_001350112.1
CHMP7	NM_001317899.2		c.521C>G	p.Ser174Cys	missense	Exon 6 of 10	NP_001304828.1	B3KRZ9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHMP7	ENST00000397677.6	TSL:1 MANE Select	c.851C>G	p.Ser284Cys	missense	Exon 7 of 11	ENSP00000380794.1	Q8WUX9-1
CHMP7	ENST00000313219.8	TSL:1	c.851C>G	p.Ser284Cys	missense	Exon 6 of 10	ENSP00000324491.7	Q8WUX9-1
CHMP7	ENST00000523091.5	TSL:1	n.821C>G		non_coding_transcript_exon	Exon 4 of 7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152232

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68056

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.040

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.26

DEOGEN2

Benign

0.15

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.079

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.74

M_CAP

Benign

0.0047

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

PhyloP100

4.1

PrimateAI

Uncertain

0.71

PROVEAN

Benign

2.0

REVEL

Benign

0.14

Sift

Benign

0.96

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.20

MutPred

0.47

Loss of phosphorylation at S284 (P = 0.0162)

MVP

0.39

MPC

0.60

ClinPred

0.81

GERP RS

4.0

Varity_R

0.081

gMVP

0.25

Mutation Taster

=94/6

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over