chr20-62817114-G-A

Position:

chr20-62817114-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001853.4(COL9A3):c.50G>A(p.Gly17Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,399,514 control chromosomes in the GnomAD database, including 15,911 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1315 hom., cov: 33)

Exomes 𝑓: 0.15 ( 14596 hom. )

Consequence

COL9A3
NM_001853.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.421

Variant links:

Genes affected

COL9A3 (HGNC:2219): (collagen type IX alpha 3 chain) This gene encodes one of the three alpha chains of type IX collagen, the major collagen component of hyaline cartilage. Type IX collagen, a heterotrimeric molecule, is usually found in tissues containing type II collagen, a fibrillar collagen. Mutations in this gene are associated with multiple epiphyseal dysplasia type 3. [provided by RefSeq, Jan 2010]

COL9A3 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=0.0021308362).

BP6

Variant 20-62817114-G-A is Benign according to our data. Variant chr20-62817114-G-A is described in ClinVar as [Benign]. Clinvar id is 193218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62817114-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL9A3	NM_001853.4 link	c.50G>A	p.Gly17Glu	missense_variant	1/32	ENST00000649368.1	NP_001844.3	Q14050

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL9A3	ENST00000649368.1 link	c.50G>A	p.Gly17Glu	missense_variant	1/32		NM_001853.4	ENSP00000496793.1		Q14050
COL9A3	ENST00000477612.5 link	n.75-453G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19055

AN:

151338

Hom.:

1314

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0994

Gnomad AMI

AF:

0.0746

Gnomad AMR

AF:

0.0977

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.0346

Gnomad SAS

AF:

0.0700

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.123

GnomAD3 exomes

AF:

0.105

AC:

7842

AN:

74786

Hom.:

570

AF XY:

0.106

AC XY:

4564

AN XY:

43216

show subpopulations

Gnomad AFR exome

AF:

0.0977

Gnomad AMR exome

AF:

0.0555

Gnomad ASJ exome

AF:

0.0988

Gnomad EAS exome

AF:

0.0366

Gnomad SAS exome

AF:

0.0660

Gnomad FIN exome

AF:

0.153

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.121

GnomAD4 exome

AF:

0.148

AC:

184420

AN:

1248068

Hom.:

14596

Cov.:

AF XY:

0.146

AC XY:

89540

AN XY:

615008

show subpopulations

Gnomad4 AFR exome

AF:

0.0983

Gnomad4 AMR exome

AF:

0.0650

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.0227

Gnomad4 SAS exome

AF:

0.0677

Gnomad4 FIN exome

AF:

0.154

Gnomad4 NFE exome

AF:

0.161

Gnomad4 OTH exome

AF:

0.129

GnomAD4 genome

AF:

0.126

AC:

19055

AN:

151446

Hom.:

1315

Cov.:

AF XY:

0.123

AC XY:

9118

AN XY:

74006

show subpopulations

Gnomad4 AFR

AF:

0.0993

Gnomad4 AMR

AF:

0.0977

Gnomad4 ASJ

AF:

0.103

Gnomad4 EAS

AF:

0.0343

Gnomad4 SAS

AF:

0.0702

Gnomad4 FIN

AF:

0.161

Gnomad4 NFE

AF:

0.156

Gnomad4 OTH

AF:

0.121

Alfa

AF:

0.134

Hom.:

183

Bravo

AF:

0.120

TwinsUK

AF:

0.166

AC:

616

ALSPAC

AF:

0.159

AC:

611

ExAC

AF:

0.0663

AC:

4505

Asia WGS

AF:

0.0400

AC:

129

AN:

3212

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 05, 2017	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 272/2178=12.48% -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 05, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Epiphyseal dysplasia, multiple, 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jul 18, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0070

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.26

.;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.2

L;L

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.0

.;N

REVEL

Uncertain

0.35

Sift

Benign

0.28

.;T

Sift4G

Benign

0.37

.;T

Polyphen

0.079

B;B

Vest4

0.17

MPC

0.091

ClinPred

0.00070

GERP RS

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.086

gMVP

0.58

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