rs2294995

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001853.4(COL9A3):c.1740T>C(p.Pro580=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 1,611,778 control chromosomes in the GnomAD database, including 387,113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43619 hom., cov: 32)

Exomes 𝑓: 0.68 ( 343494 hom. )

Consequence

COL9A3
NM_001853.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.940

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 20-62837219-T-C is Benign according to our data. Variant chr20-62837219-T-C is described in ClinVar as [Benign]. Clinvar id is 258417.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62837219-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.94 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
COL9A3	NM_001853.4 linkuse as main transcript	c.1740T>C	p.Pro580=	synonymous_variant	30/32	ENST00000649368.1	NP_001844.3
COL9A3	XM_047439893.1 linkuse as main transcript	c.1917T>C	p.Pro639=	synonymous_variant	29/31		XP_047295849.1
COL9A3	XM_047439894.1 linkuse as main transcript	c.1179T>C	p.Pro393=	synonymous_variant	30/32		XP_047295850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL9A3	ENST00000649368.1 linkuse as main transcript	c.1740T>C	p.Pro580=	synonymous_variant	30/32		NM_001853.4	ENSP00000496793	P1

Frequencies

GnomAD3 genomes

AF:

0.748

AC:

113705

AN:

151936

Hom.:

43553

Cov.:

show subpopulations

Gnomad AFR

AF:

0.929

Gnomad AMI

AF:

0.678

Gnomad AMR

AF:

0.699

Gnomad ASJ

AF:

0.729

Gnomad EAS

AF:

0.593

Gnomad SAS

AF:

0.568

Gnomad FIN

AF:

0.681

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.687

Gnomad OTH

AF:

0.733

GnomAD3 exomes

AF:

0.681

AC:

168289

AN:

247034

Hom.:

58133

AF XY:

0.674

AC XY:

90668

AN XY:

134500

show subpopulations

Gnomad AFR exome

AF:

0.936

Gnomad AMR exome

AF:

0.664

Gnomad ASJ exome

AF:

0.712

Gnomad EAS exome

AF:

0.598

Gnomad SAS exome

AF:

0.591

Gnomad FIN exome

AF:

0.679

Gnomad NFE exome

AF:

0.688

Gnomad OTH exome

AF:

0.683

GnomAD4 exome

AF:

0.684

AC:

998414

AN:

1459724

Hom.:

343494

Cov.:

AF XY:

0.681

AC XY:

494259

AN XY:

726294

show subpopulations

Gnomad4 AFR exome

AF:

0.939

Gnomad4 AMR exome

AF:

0.668

Gnomad4 ASJ exome

AF:

0.711

Gnomad4 EAS exome

AF:

0.603

Gnomad4 SAS exome

AF:

0.593

Gnomad4 FIN exome

AF:

0.682

Gnomad4 NFE exome

AF:

0.685

Gnomad4 OTH exome

AF:

0.695

GnomAD4 genome

AF:

0.749

AC:

113837

AN:

152054

Hom.:

43619

Cov.:

AF XY:

0.742

AC XY:

55166

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.929

Gnomad4 AMR

AF:

0.699

Gnomad4 ASJ

AF:

0.729

Gnomad4 EAS

AF:

0.593

Gnomad4 SAS

AF:

0.569

Gnomad4 FIN

AF:

0.681

Gnomad4 NFE

AF:

0.687

Gnomad4 OTH

AF:

0.733

Alfa

AF:

0.693

Hom.:

17491

Bravo

AF:

0.762

Asia WGS

AF:

0.651

AC:

2266

AN:

3478

EpiCase

AF:

0.694

EpiControl

AF:

0.695

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Epiphyseal dysplasia, multiple, 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.79

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

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