NM_001853.4:c.546C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001853.4(COL9A3):c.546C>T(p.Pro182Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,599,646 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 7 hom., cov: 33)

Exomes 𝑓: 0.012 ( 138 hom. )

Consequence

COL9A3
NM_001853.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -5.76

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 20-62824471-C-T is Benign according to our data. Variant chr20-62824471-C-T is described in ClinVar as [Benign]. Clinvar id is 258428.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.76 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00707 (1076/152184) while in subpopulation NFE AF= 0.0121 (820/67924). AF 95% confidence interval is 0.0114. There are 7 homozygotes in gnomad4. There are 464 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A3	NM_001853.4 link	c.546C>T	p.Pro182Pro	synonymous_variant	Exon 11 of 32	ENST00000649368.1	NP_001844.3	Q14050

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A3	ENST00000649368.1 link	c.546C>T	p.Pro182Pro	synonymous_variant	Exon 11 of 32		NM_001853.4	ENSP00000496793.1		Q14050

Frequencies

GnomAD3 genomes

AF:

0.00708

AC:

1077

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00222

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.00733

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00592

AC:

1335

AN:

225496

Hom.:

AF XY:

0.00580

AC XY:

709

AN XY:

122224

show subpopulations

Gnomad AFR exome

AF:

0.00195

Gnomad AMR exome

AF:

0.00541

Gnomad ASJ exome

AF:

0.00168

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00178

Gnomad FIN exome

AF:

0.00112

Gnomad NFE exome

AF:

0.00994

Gnomad OTH exome

AF:

0.00841

GnomAD4 exome

AF:

0.0119

AC:

17271

AN:

1447462

Hom.:

138

Cov.:

AF XY:

0.0113

AC XY:

8151

AN XY:

718984

show subpopulations

Gnomad4 AFR exome

AF:

0.00213

Gnomad4 AMR exome

AF:

0.00550

Gnomad4 ASJ exome

AF:

0.00166

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00173

Gnomad4 FIN exome

AF:

0.00160

Gnomad4 NFE exome

AF:

0.0145

Gnomad4 OTH exome

AF:

0.0116

GnomAD4 genome

AF:

0.00707

AC:

1076

AN:

152184

Hom.:

Cov.:

AF XY:

0.00624

AC XY:

464

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00222

Gnomad4 AMR

AF:

0.00732

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.0121

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00876

Hom.:

Bravo

AF:

0.00757

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

COL9A3: BP4, BP7, BS1, BS2 -

Sep 08, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 20, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 08, 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. -

Connective tissue disorder

Benign:1

Jun 18, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

2.8

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

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