rs763177718

Variant names:

• chr17-80997298-A-G
• rs763177718
• NM_024591.5:c.452A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-80997298-A-G
• chr17-80997298-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024591.5(CHMP6):​c.452A>G​(p.Glu151Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,611,242 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. E151V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: CHMP6 NM_024591.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.79
• Publications: 0 publications found

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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP6	NM_024591.5	c.452A>G	p.Glu151Gly	missense_variant	Exon 6 of 8	ENST00000325167.9	NP_078867.2
CHMP6	XM_005257668.1	c.452A>G	p.Glu151Gly	missense_variant	Exon 6 of 7		XP_005257725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHMP6	ENST00000325167.9	c.452A>G	p.Glu151Gly	missense_variant	Exon 6 of 8	1	NM_024591.5	ENSP00000317468.5
CHMP6	ENST00000572778.5	c.389A>G	p.Glu130Gly	missense_variant	Exon 5 of 6	2		ENSP00000461098.1
CHMP6	ENST00000571457.1	c.326A>G	p.Glu109Gly	missense_variant	Exon 5 of 7	3		ENSP00000461238.1
CHMP6	ENST00000572525.5	c.194A>G	p.Glu65Gly	missense_variant	Exon 6 of 8	3		ENSP00000460389.1

Frequencies

GnomAD3 genomes AF: 0.0000199 AC: 3 AN: 150716 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000298

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000810 AC: 2 AN: 246960 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000171 AC: 25 AN: 1460526 Hom.: 0 Cov.: 34 AF XY: 0.0000206 AC XY: 15 AN XY: 726592

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111138

Other (OTH) AF: 0.0000166 AC: 1 AN: 60296

GnomAD4 genome AF: 0.0000199 AC: 3 AN: 150716 Hom.: 0 Cov.: 32 AF XY: 0.0000272 AC XY: 2 AN XY: 73628

African (AFR) AF: 0.0000242 AC: 1 AN: 41264

American (AMR) AF: 0.00 AC: 0 AN: 15020

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3416

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000298 AC: 2 AN: 67208

Other (OTH) AF: 0.00 AC: 0 AN: 2060

Alfa AF: 0.0000434 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.48	T;D;.;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.97	D;D;D;D
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.60	D;D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.7	.;M;.;.
PhyloP100		8.8
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-5.8	.;D;.;.
REVEL	Uncertain	0.56
Sift	Uncertain	0.014	.;D;.;.
Sift4G	Uncertain	0.0070	D;T;T;D
Polyphen		0.86	.;P;.;.
Vest4		0.78
MutPred		0.41		.;Loss of solvent accessibility (P = 0.0187);.;.;
MVP		0.56
MPC		0.42
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.62
gMVP		0.74
Mutation Taster		=45/55	disease causing

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: rs763177718; hg19: chr17-78971098;