17-80994646-C-G

Variant names:

• chr17-80994646-C-G
• rs778694132
• NM_024591.5:c.129C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_024591.5(CHMP6):​c.129C>G​(p.Arg43Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000209 in 1,432,478 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. Synonymous variant affecting the same amino acid position (i.e. R43R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CHMP6 NM_024591.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

Genes affected

CHMP6 (HGNC:25675): (charged multivesicular body protein 6) This gene encodes a member of the chromatin-modifying protein/charged multivesicular body protein family. Proteins in this family are part of the ESCRT-III (endosomal sorting complex required for transport III) which degrades surface receptors, and in biosynthesis of endosomes. [provided by RefSeq, Mar 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=-1.54 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP6	NM_024591.5	c.129C>G	p.Arg43Arg	synonymous_variant	Exon 2 of 8	ENST00000325167.9	NP_078867.2
CHMP6	XM_005257668.1	c.129C>G	p.Arg43Arg	synonymous_variant	Exon 2 of 7		XP_005257725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHMP6	ENST00000325167.9	c.129C>G	p.Arg43Arg	synonymous_variant	Exon 2 of 8	1	NM_024591.5	ENSP00000317468.5
CHMP6	ENST00000572778.5	c.66C>G	p.Arg22Arg	synonymous_variant	Exon 1 of 6	2		ENSP00000461098.1
CHMP6	ENST00000571457.1	c.3C>G	p.Arg1Arg	synonymous_variant	Exon 1 of 7	3		ENSP00000461238.1
CHMP6	ENST00000572525.5	c.-130C>G		5_prime_UTR_variant	Exon 2 of 8	3		ENSP00000460389.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000521 AC: 1 AN: 192048 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000672

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000209 AC: 3 AN: 1432478 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 709696

African (AFR) AF: 0.00 AC: 0 AN: 33028

American (AMR) AF: 0.00 AC: 0 AN: 39392

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25450

East Asian (EAS) AF: 0.0000779 AC: 3 AN: 38514

South Asian (SAS) AF: 0.00 AC: 0 AN: 81708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099730

Other (OTH) AF: 0.00 AC: 0 AN: 59376

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.22
DANN	Benign	0.80
PhyloP100		-1.5
PromoterAI		0.0024	Neutral

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

dbSNP: rs778694132; hg19: chr17-78968446;