rs79269394

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001853.4(COL9A3):c.1327A>G(p.Ile443Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,613,604 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0095 ( 27 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 16 hom. )

Consequence

COL9A3
NM_001853.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.26

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=0.0038558543).

BP6

Variant 20-62833023-A-G is Benign according to our data. Variant chr20-62833023-A-G is described in ClinVar as [Benign]. Clinvar id is 258405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00951 (1449/152298) while in subpopulation AFR AF= 0.0309 (1283/41550). AF 95% confidence interval is 0.0295. There are 27 homozygotes in gnomad4. There are 689 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A3	NM_001853.4 link	c.1327A>G	p.Ile443Val	missense_variant	Exon 26 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.1327A>G	p.Ile443Val	missense_variant	Exon 26 of 32		NM_001853.4	ENSP00000496793.1		Q14050

Frequencies

GnomAD3 genomes

AF:

0.00949

AC:

1444

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0308

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00262

AC:

659

AN:

251102

Hom.:

AF XY:

0.00213

AC XY:

289

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.0320

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.0000994

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000361

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00111

AC:

1620

AN:

1461306

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

736

AN XY:

726988

show subpopulations

Gnomad4 AFR exome

AF:

0.0291

Gnomad4 AMR exome

AF:

0.00309

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000273

Gnomad4 OTH exome

AF:

0.00287

GnomAD4 genome

AF:

0.00951

AC:

1449

AN:

152298

Hom.:

Cov.:

AF XY:

0.00925

AC XY:

689

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0309

Gnomad4 AMR

AF:

0.00765

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00232

Hom.:

Bravo

AF:

0.0111

ESP6500AA

AF:

0.0304

AC:

134

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00334

AC:

405

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.33

CADD

Benign

0.61

DANN

Benign

0.69

DEOGEN2

Benign

0.00043

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.67

.;T

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.48

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

0.16

.;N

REVEL

Benign

0.21

Sift

Benign

0.80

.;T

Sift4G

Benign

0.32

.;T

Polyphen

0.0050

B;B

Vest4

0.23

MVP

0.55

MPC

0.086

ClinPred

0.00088

GERP RS

-1.8

Varity_R

0.026

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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