chr8-23260146-T-G

Variant names:

• chr8-23260146-T-G
• rs769874873
• NM_152272.5:c.1123T>G

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.1123T>G​(p.Phe375Val) variant causes a missense, splice region 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. 16/22 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. F375I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHMP7 NM_152272.5 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.645
• 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=0.081355035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP7	NM_152272.5	c.1123T>G	p.Phe375Val	missense_variant, splice_region_variant	Exon 10 of 11	ENST00000397677.6	NP_689485.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHMP7	ENST00000397677.6	c.1123T>G	p.Phe375Val	missense_variant, splice_region_variant	Exon 10 of 11	1	NM_152272.5	ENSP00000380794.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Benign	0.87
DEOGEN2	Benign	0.14	T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.69	.;T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.081	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.90	N;N
PhyloP100		0.65
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.22	N;N
REVEL	Benign	0.12
Sift	Benign	0.96	T;T
Sift4G	Benign	0.58	T;T
Polyphen		0.0	B;B
Vest4		0.17
MutPred		0.40		Loss of catalytic residue at F375 (P = 0.0909);Loss of catalytic residue at F375 (P = 0.0909);
MVP		0.58
MPC		0.81
ClinPred		0.23	T
GERP RS		4.5
Varity_R		0.076
gMVP		0.23
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

dbSNP: rs769874873; hg19: chr8-23117659;