chr17-80997010-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024591.5(CHMP6):​c.352A>T​(p.Met118Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. M118V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CHMP6
NM_024591.5 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.79

Publications

0 publications found
Variant links:
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]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18583426).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CHMP6NM_024591.5 linkc.352A>T p.Met118Leu missense_variant Exon 5 of 8 ENST00000325167.9 NP_078867.2 Q96FZ7
CHMP6XM_005257668.1 linkc.352A>T p.Met118Leu missense_variant Exon 5 of 7 XP_005257725.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CHMP6ENST00000325167.9 linkc.352A>T p.Met118Leu missense_variant Exon 5 of 8 1 NM_024591.5 ENSP00000317468.5 Q96FZ7
CHMP6ENST00000572778.5 linkc.289A>T p.Met97Leu missense_variant Exon 4 of 6 2 ENSP00000461098.1 I3L4A1
CHMP6ENST00000571457.1 linkc.226A>T p.Met76Leu missense_variant Exon 4 of 7 3 ENSP00000461238.1 I3L4G8
CHMP6ENST00000572525.5 linkc.94A>T p.Met32Leu missense_variant Exon 5 of 8 3 ENSP00000460389.1 I3L3E4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461296
Hom.:
0
Cov.:
40
AF XY:
0.00000138
AC XY:
1
AN XY:
726948
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33470
American (AMR)
AF:
0.00
AC:
0
AN:
44666
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26102
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86190
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53346
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5712
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111746
Other (OTH)
AF:
0.00
AC:
0
AN:
60364
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.0020
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
19
DANN
Benign
0.90
DEOGEN2
Benign
0.24
T;T;.;.
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.11
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.92
D;D;D;D
M_CAP
Benign
0.082
D
MetaRNN
Benign
0.19
T;T;T;T
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
1.4
.;L;.;.
PhyloP100
6.8
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.95
.;N;.;.
REVEL
Benign
0.19
Sift
Benign
0.39
.;T;.;.
Sift4G
Benign
0.38
T;T;T;T
Polyphen
0.0080
.;B;.;.
Vest4
0.58
MutPred
0.54
.;Loss of ubiquitination at K113 (P = 0.0598);.;.;
MVP
0.58
MPC
0.072
ClinPred
0.39
T
GERP RS
4.1
Varity_R
0.16
gMVP
0.54

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

Other links and lift over

dbSNP: rs762369762; hg19: chr17-78970810; API