rs367935751

Variant names:

• chr17-80994650-C-A
• rs367935751
• NM_024591.5:c.133C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-80994650-C-A
• chr17-80994650-C-T

Variant summary

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

The NM_024591.5(CHMP6):​c.133C>A​(p.Arg45Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R45H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHMP6 NM_024591.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• 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.133C>A	p.Arg45Ser	missense_variant	Exon 2 of 8	ENST00000325167.9	NP_078867.2
CHMP6	XM_005257668.1	c.133C>A	p.Arg45Ser	missense_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.133C>A	p.Arg45Ser	missense_variant	Exon 2 of 8	1	NM_024591.5	ENSP00000317468.5
CHMP6	ENST00000572778.5	c.70C>A	p.Arg24Ser	missense_variant	Exon 1 of 6	2		ENSP00000461098.1
CHMP6	ENST00000571457.1	c.7C>A	p.Arg3Ser	missense_variant	Exon 1 of 7	3		ENSP00000461238.1
CHMP6	ENST00000572525.5	c.-126C>A		5_prime_UTR_variant	Exon 2 of 8	3		ENSP00000460389.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;.;.
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.91	D;D;T
M_CAP	Pathogenic	0.64	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Uncertain	0.0099	D
MutationAssessor	Uncertain	2.5	M;.;.
PhyloP100		0.096
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-5.4	D;.;.
REVEL	Uncertain	0.54
Sift	Uncertain	0.0090	D;.;.
Sift4G	Uncertain	0.041	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.63
MutPred		0.43		Gain of phosphorylation at R45 (P = 0.0203);.;.;
MVP		0.78
MPC		0.41
ClinPred		0.99	D
GERP RS		2.0
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.87
gMVP		0.57

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: rs367935751; hg19: chr17-78968450;