2-86529157-G-C

Variant names:

• chr2-86529157-G-C
• rs9284788
• NM_016079.4:c.286+61C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016079.4(CHMP3):​c.286+61C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000078 in 1,282,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: CHMP3 NM_016079.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 0 publications found

Genes affected

CHMP3 (HGNC:29865): (charged multivesicular body protein 3) This gene encodes a protein that sorts transmembrane proteins into lysosomes/vacuoles via the multivesicular body (MVB) pathway. This protein, along with other soluble coiled-coil containing proteins, forms part of the ESCRT-III protein complex that binds to the endosomal membrane and recruits additional cofactors for protein sorting into the MVB. This protein may also co-immunoprecipitate with a member of the IFG-binding protein superfamily. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the upstream ring finger protein 103 (RNF103) gene. [provided by RefSeq, Nov 2010]

RNF103-CHMP3 (HGNC:38847): (RNF103-CHMP3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring RNF103 (ring finger protein 103) and CHMP3 (charged multivesicular body protein 3) genes. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP3	NM_016079.4	c.286+61C>G		intron_variant	Intron 3 of 5	ENST00000263856.9	NP_057163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHMP3	ENST00000263856.9	c.286+61C>G		intron_variant	Intron 3 of 5	1	NM_016079.4	ENSP00000263856.4
RNF103-CHMP3	ENST00000604011.5	c.373+61C>G		intron_variant	Intron 5 of 7	2		ENSP00000474823.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.80e-7 AC: 1 AN: 1282354 Hom.: 0 AF XY: 0.00000160 AC XY: 1 AN XY: 626534

African (AFR) AF: 0.00 AC: 0 AN: 26956

American (AMR) AF: 0.00 AC: 0 AN: 22740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19248

East Asian (EAS) AF: 0.0000304 AC: 1 AN: 32872

South Asian (SAS) AF: 0.00 AC: 0 AN: 55728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47048

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5050

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1020420

Other (OTH) AF: 0.00 AC: 0 AN: 52292

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.63
PhyloP100		-0.081

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: rs9284788; hg19: chr2-86756280;