17-80994680-G-A

Position:

chr17-80994680-G-A

Variant summary

Our verdict is Benign. Variant got -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 (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 41 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHMP6	NM_024591.5 linkuse as main transcript	c.163G>A	p.Gly55Ser	missense_variant	2/8	ENST00000325167.9	NP_078867.2	Q96FZ7
CHMP6	XM_005257668.1 linkuse as main transcript	c.163G>A	p.Gly55Ser	missense_variant	2/7		XP_005257725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHMP6	ENST00000325167.9 linkuse as main transcript	c.163G>A	p.Gly55Ser	missense_variant	2/8	1	NM_024591.5	ENSP00000317468.5	Q96FZ7
CHMP6	ENST00000572778.5 linkuse as main transcript	c.100G>A	p.Gly34Ser	missense_variant	1/6	2		ENSP00000461098.1	I3L4A1
CHMP6	ENST00000571457.1 linkuse as main transcript	c.37G>A	p.Gly13Ser	missense_variant	1/7	3		ENSP00000461238.1	I3L4G8
CHMP6	ENST00000572525.5 linkuse as main transcript	c.-96G>A		5_prime_UTR_variant	2/8	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

GnomAD3 exomes

AF:

0.00151

AC:

259

AN:

171032

Hom.:

AF XY:

0.00123

AC XY:

114

AN XY:

93060

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 SAS 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

Gnomad4 AFR exome

AF:

0.0174

Gnomad4 AMR exome

AF:

0.00200

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000744

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000503

Gnomad4 OTH exome

AF:

0.00192

GnomAD4 genome

AF:

0.0119

AC:

1816

AN:

152130

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

848

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0413

Gnomad4 AMR

AF:

0.00458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00803

Alfa

AF:

0.00322

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

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

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;.;.

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.46

gMVP

0.48

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over