8-23255402-G-C

Variant names:

• chr8-23255402-G-C
• NM_152272.5:c.627G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152272.5(CHMP7):​c.627G>C​(p.Arg209Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHMP7 NM_152272.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.287
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26435596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP7	NM_152272.5	c.627G>C	p.Arg209Ser	missense_variant	Exon 4 of 11	ENST00000397677.6	NP_689485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHMP7	ENST00000397677.6	c.627G>C	p.Arg209Ser	missense_variant	Exon 4 of 11	1	NM_152272.5	ENSP00000380794.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.627G>C (p.R209S) alteration is located in exon 4 (coding exon 3) of the CHMP7 gene. This alteration results from a G to C substitution at nucleotide position 627, causing the arginine (R) at amino acid position 209 to be replaced by a serine (S). 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	0.62
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.062	T;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.91	.;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.90	L;L
PhyloP100		-0.29
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.28
Sift	Uncertain	0.023	D;D
Sift4G	Uncertain	0.038	D;D
Polyphen		0.0080	B;B
Vest4		0.67
MutPred		0.34		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.50
MPC		0.72
ClinPred		0.63	D
GERP RS		-1.9
Varity_R		0.24
gMVP		0.37
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr8-23112915;