chr20-62840573-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001853.4(COL9A3):c.1896C>T(p.Asp632Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 1,612,582 control chromosomes in the GnomAD database, including 171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 9 hom., cov: 33)

Exomes 𝑓: 0.013 ( 162 hom. )

Consequence

COL9A3
NM_001853.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.91

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=-0.56).

BP6

Variant 20-62840573-C-T is Benign according to our data. Variant chr20-62840573-C-T is described in ClinVar as [Benign]. Clinvar id is 258419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62840573-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.91 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00774 (1179/152342) while in subpopulation NFE AF= 0.0138 (941/68030). AF 95% confidence interval is 0.0131. There are 9 homozygotes in gnomad4. There are 536 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A3	NM_001853.4 link	c.1896C>T	p.Asp632Asp	synonymous_variant	Exon 32 of 32	ENST00000649368.1	NP_001844.3	Q14050
COL9A3	XM_047439893.1 link	c.2073C>T	p.Asp691Asp	synonymous_variant	Exon 31 of 31		XP_047295849.1
COL9A3	XM_047439894.1 link	c.1335C>T	p.Asp445Asp	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.1896C>T	p.Asp632Asp	synonymous_variant	Exon 32 of 32		NM_001853.4	ENSP00000496793.1		Q14050

Frequencies

GnomAD3 genomes

AF:

0.00775

AC:

1179

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0138

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00690

AC:

1720

AN:

249354

Hom.:

AF XY:

0.00663

AC XY:

897

AN XY:

135328

show subpopulations

Gnomad AFR exome

AF:

0.00271

Gnomad AMR exome

AF:

0.00408

Gnomad ASJ exome

AF:

0.0000997

Gnomad EAS exome

AF:

0.000491

Gnomad SAS exome

AF:

0.00209

Gnomad FIN exome

AF:

0.00227

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.00722

GnomAD4 exome

AF:

0.0131

AC:

19061

AN:

1460240

Hom.:

162

Cov.:

AF XY:

0.0127

AC XY:

9208

AN XY:

726484

show subpopulations

Gnomad4 AFR exome

AF:

0.00236

Gnomad4 AMR exome

AF:

0.00391

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00229

Gnomad4 FIN exome

AF:

0.00300

Gnomad4 NFE exome

AF:

0.0161

Gnomad4 OTH exome

AF:

0.00934

GnomAD4 genome

AF:

0.00774

AC:

1179

AN:

152342

Hom.:

Cov.:

AF XY:

0.00719

AC XY:

536

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00238

Gnomad4 AMR

AF:

0.00529

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.0138

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.00764

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0137

EpiControl

AF:

0.0105

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Jul 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

COL9A3: BP4, BP7, BS1, BS2 -

Mar 30, 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

- -

Jul 03, 2019

GeneDx

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

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Connective tissue disorder

Benign:1

Feb 07, 2022

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

-0.56

CADD

Benign

0.13

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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