8-23246942-C-A

Variant names:

• chr8-23246942-C-A
• rs1801721241
• NM_152272.5:c.247C>A

Variant summary

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

The NM_152272.5(CHMP7):​c.247C>A​(p.Arg83Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000129 in 1,556,248 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. R83C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CHMP7 NM_152272.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.49
• 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, 0.831

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.247C>A	p.Arg83Ser	missense	Exon 2 of 11	NP_689485.1	Q8WUX9-1
	CHMP7	NM_001363183.2		c.247C>A	p.Arg83Ser	missense	Exon 1 of 9	NP_001350112.1
	CHMP7	NM_001317899.2		c.-32+118C>A		intron	N/A	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.247C>A	p.Arg83Ser	missense	Exon 2 of 11	ENSP00000380794.1	Q8WUX9-1
	CHMP7	ENST00000313219.8	TSL:1	c.247C>A	p.Arg83Ser	missense	Exon 1 of 10	ENSP00000324491.7	Q8WUX9-1
	CHMP7	ENST00000880275.1		c.247C>A	p.Arg83Ser	missense	Exon 2 of 11	ENSP00000550334.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1404052 Hom.: 0 Cov.: 36 AF XY: 0.00000144 AC XY: 1 AN XY: 693776

African (AFR) AF: 0.00 AC: 0 AN: 32334

American (AMR) AF: 0.0000275 AC: 1 AN: 36382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25204

East Asian (EAS) AF: 0.00 AC: 0 AN: 36894

South Asian (SAS) AF: 0.00 AC: 0 AN: 80128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44984

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5124

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084682

Other (OTH) AF: 0.00 AC: 0 AN: 58320

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152196 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.0000654 AC: 1 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.5
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.012	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.76	P
Vest4		0.49
MutPred		0.79		Loss of MoRF binding (P = 0.0211)
MVP		0.84
MPC		0.73
ClinPred		0.99	D
GERP RS		4.3
PromoterAI		-0.045	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.95
Mutation Taster		=54/46	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: rs1801721241; hg19: chr8-23104455;