20-62819953-C-T

Position:

chr20-62819953-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.280C>T(p.Pro94Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00988 in 1,612,860 control chromosomes in the GnomAD database, including 1,035 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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 0.046 ( 543 hom., cov: 33)

Exomes 𝑓: 0.0061 ( 492 hom. )

Consequence

COL9A3
NM_001853.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.324

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=0.0026812851).

BP6

Variant 20-62819953-C-T is Benign according to our data. Variant chr20-62819953-C-T is described in ClinVar as [Benign]. Clinvar id is 258422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62819953-C-T is described in Lovd as [Likely_benign]. Variant chr20-62819953-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A3	NM_001853.4 linkuse as main transcript	c.280C>T	p.Pro94Ser	missense_variant	5/32	ENST00000649368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
COL9A3	ENST00000649368.1 linkuse as main transcript	c.280C>T	p.Pro94Ser	missense_variant	5/32		NM_001853.4	P1
COL9A3	ENST00000452372.2 linkuse as main transcript	c.169C>T	p.Pro57Ser	missense_variant	4/12	5
COL9A3	ENST00000477612.5 linkuse as main transcript	n.276C>T		non_coding_transcript_exon_variant	5/12	3
COL9A3	ENST00000489045.5 linkuse as main transcript	n.326C>T		non_coding_transcript_exon_variant	4/14	5

Frequencies

GnomAD3 genomes

AF:

0.0463

AC:

7036

AN:

152110

Hom.:

539

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0217

Gnomad ASJ

AF:

0.00835

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0157

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000809

Gnomad OTH

AF:

0.0325

GnomAD3 exomes

AF:

0.0145

AC:

3630

AN:

249832

Hom.:

226

AF XY:

0.0114

AC XY:

1550

AN XY:

135412

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.00707

Gnomad EAS exome

AF:

0.00109

Gnomad SAS exome

AF:

0.0149

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000614

Gnomad OTH exome

AF:

0.00883

GnomAD4 exome

AF:

0.00607

AC:

8863

AN:

1460632

Hom.:

492

Cov.:

AF XY:

0.00565

AC XY:

4103

AN XY:

726632

show subpopulations

Gnomad4 AFR exome

AF:

0.163

Gnomad4 AMR exome

AF:

0.0119

Gnomad4 ASJ exome

AF:

0.00696

Gnomad4 EAS exome

AF:

0.000831

Gnomad4 SAS exome

AF:

0.0142

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000518

Gnomad4 OTH exome

AF:

0.0133

GnomAD4 genome

AF:

0.0464

AC:

7068

AN:

152228

Hom.:

543

Cov.:

AF XY:

0.0447

AC XY:

3327

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.156

Gnomad4 AMR

AF:

0.0216

Gnomad4 ASJ

AF:

0.00835

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0157

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.0345

Alfa

AF:

0.0156

Hom.:

129

Bravo

AF:

0.0537

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.150

AC:

662

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.0171

AC:

2075

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 22, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

T;T;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.64

.;T;T

MetaRNN

Benign

0.0027

T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.6

M;M;.

MutationTaster

Benign

0.69

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.7

.;N;N

REVEL

Uncertain

0.33

Sift

Benign

0.16

.;T;T

Sift4G

Uncertain

0.051

.;T;D

Polyphen

0.26

B;B;.

Vest4

0.10

MPC

0.071

ClinPred

0.025

GERP RS

3.6

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.7

Varity_R

0.099

gMVP

0.59

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