8-23246714-G-A

Variant names:

• chr8-23246714-G-A
• NM_152272.5:c.19G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152272.5(CHMP7):​c.19G>A​(p.Glu7Lys) 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. 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: 3.36
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23993826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP7	NM_152272.5	c.19G>A	p.Glu7Lys	missense_variant	Exon 2 of 11	ENST00000397677.6	NP_689485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHMP7	ENST00000397677.6	c.19G>A	p.Glu7Lys	missense_variant	Exon 2 of 11	1	NM_152272.5	ENSP00000380794.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.19G>A (p.E7K) alteration is located in exon 2 (coding exon 1) of the CHMP7 gene. This alteration results from a G to A substitution at nucleotide position 19, causing the glutamic acid (E) at amino acid position 7 to be replaced by a lysine (K). 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	0.13
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T;T;T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.84	.;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.1	L;L;.
PhyloP100		3.4
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-0.43	N;N;N
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D;D;D
Sift4G	Benign	0.14	T;T;T
Polyphen		0.61	P;P;.
Vest4		0.34
MutPred		0.094		Gain of ubiquitination at E7 (P = 0.0066);Gain of ubiquitination at E7 (P = 0.0066);Gain of ubiquitination at E7 (P = 0.0066);
MVP		0.62
MPC		0.69
ClinPred		0.90	D
GERP RS		5.8
PromoterAI		0.11	Neutral
Varity_R		0.57
gMVP		0.70
Mutation Taster		=88/12	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: chr8-23104227;