rs1048100

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001853.4(COL9A3):c.2044C>A(p.Arg682Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0894 in 1,571,590 control chromosomes in the GnomAD database, including 9,005 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2524 hom., cov: 32)

Exomes 𝑓: 0.083 ( 6481 hom. )

Consequence

COL9A3
NM_001853.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.811

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 20-62840721-C-A is Benign according to our data. Variant chr20-62840721-C-A is described in ClinVar as [Benign]. Clinvar id is 258420.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62840721-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.811 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A3	NM_001853.4 link	c.2044C>A	p.Arg682Arg	synonymous_variant	Exon 32 of 32	ENST00000649368.1	NP_001844.3	Q14050
COL9A3	XM_047439893.1 link	c.2221C>A	p.Arg741Arg	synonymous_variant	Exon 31 of 31		XP_047295849.1
COL9A3	XM_047439894.1 link	c.1483C>A	p.Arg495Arg	synonymous_variant	Exon 32 of 32		XP_047295850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A3	ENST00000649368.1 link	c.2044C>A	p.Arg682Arg	synonymous_variant	Exon 32 of 32		NM_001853.4	ENSP00000496793.1		Q14050

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22664

AN:

151974

Hom.:

2521

Cov.:

show subpopulations

Gnomad AFR

AF:

0.313

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.0948

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.0882

Gnomad FIN

AF:

0.0660

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.0816

Gnomad OTH

AF:

0.150

GnomAD3 exomes

AF:

0.0975

AC:

17463

AN:

179196

Hom.:

1230

AF XY:

0.0938

AC XY:

8951

AN XY:

95426

show subpopulations

Gnomad AFR exome

AF:

0.315

Gnomad AMR exome

AF:

0.0588

Gnomad ASJ exome

AF:

0.0981

Gnomad EAS exome

AF:

0.156

Gnomad SAS exome

AF:

0.0774

Gnomad FIN exome

AF:

0.0661

Gnomad NFE exome

AF:

0.0825

Gnomad OTH exome

AF:

0.0959

GnomAD4 exome

AF:

0.0830

AC:

117838

AN:

1419498

Hom.:

6481

Cov.:

AF XY:

0.0828

AC XY:

58101

AN XY:

702042

show subpopulations

Gnomad4 AFR exome

AF:

0.325

Gnomad4 AMR exome

AF:

0.0627

Gnomad4 ASJ exome

AF:

0.0984

Gnomad4 EAS exome

AF:

0.102

Gnomad4 SAS exome

AF:

0.0785

Gnomad4 FIN exome

AF:

0.0679

Gnomad4 NFE exome

AF:

0.0751

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.149

AC:

22701

AN:

152092

Hom.:

2524

Cov.:

AF XY:

0.145

AC XY:

10775

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.313

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.0948

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.0883

Gnomad4 FIN

AF:

0.0660

Gnomad4 NFE

AF:

0.0816

Gnomad4 OTH

AF:

0.152

Alfa

AF:

0.0871

Hom.:

1346

Bravo

AF:

0.161

Asia WGS

AF:

0.135

AC:

469

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 15, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

0.53

DANN

Benign

0.61

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