chr17-80994680-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024591.5(CHMP6):c.163G>A(p.Gly55Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,571,004 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 41 hom., cov: 32)

Exomes 𝑓: 0.00056 ( 17 hom. )

Consequence

CHMP6
NM_024591.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.29

Publications

2 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]

CHMP6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008747071).

BP6

Variant 17-80994680-G-A is Benign according to our data. Variant chr17-80994680-G-A is described in ClinVar as [Benign]. Clinvar id is 777275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0119 (1816/152130) while in subpopulation AFR AF = 0.0413 (1713/41436). AF 95% confidence interval is 0.0397. There are 41 homozygotes in GnomAd4. There are 848 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHMP6	NM_024591.5 link	c.163G>A	p.Gly55Ser	missense_variant	Exon 2 of 8	ENST00000325167.9	NP_078867.2	Q96FZ7
CHMP6	XM_005257668.1 link	c.163G>A	p.Gly55Ser	missense_variant	Exon 2 of 7		XP_005257725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHMP6	ENST00000325167.9 link	c.163G>A	p.Gly55Ser	missense_variant	Exon 2 of 8	1	NM_024591.5	ENSP00000317468.5	Q96FZ7
CHMP6	ENST00000572778.5 link	c.100G>A	p.Gly34Ser	missense_variant	Exon 1 of 6	2		ENSP00000461098.1	I3L4A1
CHMP6	ENST00000571457.1 link	c.37G>A	p.Gly13Ser	missense_variant	Exon 1 of 7	3		ENSP00000461238.1	I3L4G8
CHMP6	ENST00000572525.5 link	c.-96G>A		5_prime_UTR_variant	Exon 2 of 8	3		ENSP00000460389.1	I3L3E4

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1816

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0415

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00812

GnomAD2 exomes

AF:

0.00151

AC:

259

AN:

171032

AF XY:

0.00123

show subpopulations

Gnomad AFR exome

AF:

0.0258

Gnomad AMR exome

AF:

0.000902

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000854

Gnomad OTH exome

AF:

0.000666

GnomAD4 exome

AF:

0.000562

AC:

798

AN:

1418874

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

358

AN XY:

702328

show subpopulations

African (AFR)

AF:

0.0174

AC:

540

AN:

31006

American (AMR)

AF:

0.00200

AC:

AN:

37540

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25248

East Asian (EAS)

AF:

0.00

AC:

AN:

37944

South Asian (SAS)

AF:

0.0000744

AC:

AN:

80680

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48870

Middle Eastern (MID)

AF:

0.00159

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

0.0000503

AC:

AN:

1093170

Other (OTH)

AF:

0.00192

AC:

113

AN:

58748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

112

149

186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0119

AC:

1816

AN:

152130

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

848

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0413

AC:

1713

AN:

41436

American (AMR)

AF:

0.00458

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68010

Other (OTH)

AF:

0.00803

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

183

274

366

457

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00374

Hom.:

Bravo

AF:

0.0144

ESP6500AA

AF:

0.0390

AC:

165

ESP6500EA

AF:

0.000479

AC:

ExAC

AF:

0.00262

AC:

303

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

D;.;.

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D;D

MetaRNN

Benign

0.0087

T;T;T

MetaSVM

Uncertain

-0.096

MutationAssessor

Pathogenic

3.3

M;.;.

PhyloP100

7.3

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-4.7

D;.;.

REVEL

Uncertain

0.48

Sift

Uncertain

0.0060

D;.;.

Sift4G

Benign

0.15

T;D;D

Polyphen

1.0

D;.;.

Vest4

0.57

MVP

0.77

MPC

0.40

ClinPred

0.061

GERP RS

4.4

PromoterAI

0.0084

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.46

gMVP

0.48

Mutation Taster

=76/24

polymorphism

(source)

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

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chr17-80994680-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over