8-23246786-A-G

Variant names:

• chr8-23246786-A-G
• rs754334360
• NM_152272.5:c.91A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152272.5(CHMP7):​c.91A>G​(p.Met31Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000007 in 1,429,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. M31L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CHMP7 NM_152272.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.15
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.785

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP7	NM_152272.5	c.91A>G	p.Met31Val	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.91A>G	p.Met31Val	missense_variant	Exon 2 of 11	1	NM_152272.5	ENSP00000380794.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.00e-7 AC: 1 AN: 1429546 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 708342

African (AFR) AF: 0.00 AC: 0 AN: 32642

American (AMR) AF: 0.00 AC: 0 AN: 39750

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25542

East Asian (EAS) AF: 0.00 AC: 0 AN: 37598

South Asian (SAS) AF: 0.00 AC: 0 AN: 81848

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5600

European-Non Finnish (NFE) AF: 9.12e-7 AC: 1 AN: 1096536

Other (OTH) AF: 0.00 AC: 0 AN: 59148

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	26
DANN	Benign	0.96
DEOGEN2	Benign	0.30	T;T;T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.78	.;T;T
M_CAP	Benign	0.040	D
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Benign	-0.42	T
MutationAssessor	Uncertain	2.1	M;M;.
PhyloP100		6.2
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.010	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.54
MutPred		0.61		Loss of catalytic residue at M31 (P = 0.0031);Loss of catalytic residue at M31 (P = 0.0031);Loss of catalytic residue at M31 (P = 0.0031);
MVP		0.81
MPC		0.74
ClinPred		0.97	D
GERP RS		5.8
PromoterAI		-0.040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.70
gMVP		0.91
Mutation Taster		=55/45	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

dbSNP: rs754334360; hg19: chr8-23104299;