8-23249283-G-T

Variant names:

• chr8-23249283-G-T
• NM_152272.5:c.373G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152272.5(CHMP7):​c.373G>T​(p.Val125Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHMP7 NM_152272.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.50
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHMP7	NM_152272.5	MANE Select	c.373G>T	p.Val125Phe	missense	Exon 3 of 11	NP_689485.1	Q8WUX9-1
	CHMP7	NM_001363183.2		c.373G>T	p.Val125Phe	missense	Exon 2 of 9	NP_001350112.1
	CHMP7	NM_001317899.2		c.43G>T	p.Val15Phe	missense	Exon 2 of 10	NP_001304828.1	B3KRZ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHMP7	ENST00000397677.6	TSL:1 MANE Select	c.373G>T	p.Val125Phe	missense	Exon 3 of 11	ENSP00000380794.1	Q8WUX9-1
	CHMP7	ENST00000313219.8	TSL:1	c.373G>T	p.Val125Phe	missense	Exon 2 of 10	ENSP00000324491.7	Q8WUX9-1
	CHMP7	ENST00000880275.1		c.373G>T	p.Val125Phe	missense	Exon 3 of 11	ENSP00000550334.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.085	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.071	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.5
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.18
Sift	Uncertain	0.024	D
Sift4G	Benign	0.12	T
Polyphen		0.95	P
Vest4		0.72
MutPred		0.38		Loss of sheet (P = 0.0457)
MVP		0.63
MPC		0.84
ClinPred		0.81	D
GERP RS		5.4
Varity_R		0.26
gMVP		0.66
Mutation Taster		=82/18	polymorphism

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

Other links and lift over

hg19: chr8-23106796;