chr20-62819980-C-T

Position:

chr20-62819980-C-T

Variant summary

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

The NM_001853.4(COL9A3):c.307C>T(p.Arg103Trp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0592 in 1,612,252 control chromosomes in the GnomAD database, including 3,307 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R103Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.045 ( 214 hom., cov: 33)

Exomes 𝑓: 0.061 ( 3093 hom. )

Consequence

COL9A3
NM_001853.4 missense, splice_region

Scores

Splicing: ADA: 0.7530

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: 0.939

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=0.0063285828).

BP6

Variant 20-62819980-C-T is Benign according to our data. Variant chr20-62819980-C-T is described in ClinVar as [Benign]. Clinvar id is 17139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62819980-C-T is described in Lovd as [Benign]. Variant chr20-62819980-C-T is described in Lovd as [Likely_pathogenic].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL9A3	NM_001853.4 linkuse as main transcript	c.307C>T	p.Arg103Trp	missense_variant, splice_region_variant	5/32	ENST00000649368.1	NP_001844.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
COL9A3	ENST00000649368.1 linkuse as main transcript	c.307C>T	p.Arg103Trp	missense_variant, splice_region_variant	5/32		NM_001853.4	ENSP00000496793	P1
COL9A3	ENST00000452372.2 linkuse as main transcript	c.196C>T	p.Arg66Trp	missense_variant, splice_region_variant	4/12	5		ENSP00000394280
COL9A3	ENST00000477612.5 linkuse as main transcript	n.303C>T		splice_region_variant, non_coding_transcript_exon_variant	5/12	3
COL9A3	ENST00000489045.5 linkuse as main transcript	n.353C>T		splice_region_variant, non_coding_transcript_exon_variant	4/14	5

Frequencies

GnomAD3 genomes

AF:

0.0450

AC:

6823

AN:

151698

Hom.:

214

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0120

Gnomad AMI

AF:

0.0352

Gnomad AMR

AF:

0.0370

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.000587

Gnomad SAS

AF:

0.0295

Gnomad FIN

AF:

0.0957

Gnomad MID

AF:

0.0446

Gnomad NFE

AF:

0.0650

Gnomad OTH

AF:

0.0459

GnomAD3 exomes

AF:

0.0474

AC:

11845

AN:

249634

Hom.:

395

AF XY:

0.0488

AC XY:

6607

AN XY:

135374

show subpopulations

Gnomad AFR exome

AF:

0.0125

Gnomad AMR exome

AF:

0.0214

Gnomad ASJ exome

AF:

0.0183

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0309

Gnomad FIN exome

AF:

0.0968

Gnomad NFE exome

AF:

0.0655

Gnomad OTH exome

AF:

0.0553

GnomAD4 exome

AF:

0.0607

AC:

88695

AN:

1460438

Hom.:

3093

Cov.:

AF XY:

0.0602

AC XY:

43731

AN XY:

726546

show subpopulations

Gnomad4 AFR exome

AF:

0.00941

Gnomad4 AMR exome

AF:

0.0223

Gnomad4 ASJ exome

AF:

0.0196

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0326

Gnomad4 FIN exome

AF:

0.0933

Gnomad4 NFE exome

AF:

0.0684

Gnomad4 OTH exome

AF:

0.0484

GnomAD4 genome

AF:

0.0449

AC:

6820

AN:

151814

Hom.:

214

Cov.:

AF XY:

0.0449

AC XY:

3333

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.0119

Gnomad4 AMR

AF:

0.0370

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.000588

Gnomad4 SAS

AF:

0.0296

Gnomad4 FIN

AF:

0.0957

Gnomad4 NFE

AF:

0.0650

Gnomad4 OTH

AF:

0.0454

Alfa

AF:

0.0527

Hom.:

127

Bravo

AF:

0.0391

TwinsUK

AF:

0.0690

AC:

256

ALSPAC

AF:

0.0651

AC:

251

ESP6500AA

AF:

0.0145

AC:

ESP6500EA

AF:

0.0672

AC:

578

ExAC

AF:

0.0475

AC:

5759

Asia WGS

AF:

0.00982

AC:

AN:

3478

EpiCase

AF:

0.0583

EpiControl

AF:

0.0598

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 05, 2015	- -
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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Feb 05, 2015	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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. -

Connective tissue disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jul 18, 2022

- -

Intervertebral disc disease, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Apr 11, 2001

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.58

D;D;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Benign

0.71

LIST_S2

Pathogenic

0.97

.;D;D

MetaRNN

Benign

0.0063

T;T;T

MetaSVM

Uncertain

0.0011

MutationAssessor

Uncertain

2.4

M;M;.

MutationTaster

Benign

0.82

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.2

.;D;D

REVEL

Uncertain

0.50

Sift

Uncertain

0.0040

.;D;D

Sift4G

Uncertain

0.0030

.;D;D

Polyphen

1.0

D;D;.

Vest4

0.17

MPC

0.073

ClinPred

0.014

GERP RS

3.6

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.29

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.75

dbscSNV1_RF

Benign

0.18

SpliceAI score (max)

0.010

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