NM_001853.4:c.901-9T>C

Variant names:

• chr20-62828755-T-C
• rs74506912
• NM_001853.4:c.901-9T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001853.4(COL9A3):​c.901-9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00604 in 1,612,596 control chromosomes in the GnomAD database, including 517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0085 (72 hom., cov: 35)
  • Exomes 𝑓: 0.0058 (445 hom.)
• Consequence: COL9A3 NM_001853.4 intron
• Scores: Splicing: ADA: 0.0002385
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.72
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• epiphyseal dysplasia, multiple, 3

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Illumina, G2P, Labcorp Genetics (formerly Invitae)
• Stickler syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, ClinGen
• Stickler syndrome, type 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• multiple epiphyseal dysplasia due to collagen 9 anomaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive Stickler syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 20-62828755-T-C is Benign according to our data. Variant chr20-62828755-T-C is described in ClinVar as Benign. ClinVar VariationId is 194832.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001853.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL9A3	NM_001853.4	MANE Select	c.901-9T>C		intron	N/A	NP_001844.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL9A3	ENST00000649368.1	MANE Select	c.901-9T>C		intron	N/A	ENSP00000496793.1
	COL9A3	ENST00000463487.2	TSL:5	n.609-9T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00854 AC: 1299 AN: 152174 Hom.: 72 Cov.: 35

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0255

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00812

GnomAD2 exomes AF: 0.0197 AC: 4903 AN: 249348 AF XY: 0.0165

Gnomad AFR exome AF: 0.00125

Gnomad AMR exome AF: 0.0544

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.155

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000205

Gnomad OTH exome AF: 0.00937

GnomAD4 exome AF: 0.00578 AC: 8444 AN: 1460304 Hom.: 445 Cov.: 34 AF XY: 0.00546 AC XY: 3968 AN XY: 726458

African (AFR) AF: 0.000747 AC: 25 AN: 33478

American (AMR) AF: 0.0509 AC: 2276 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.132 AC: 5256 AN: 39692

South Asian (SAS) AF: 0.00285 AC: 246 AN: 86246

European-Finnish (FIN) AF: 0.0000192 AC: 1 AN: 52154

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5762

European-Non Finnish (NFE) AF: 0.0000810 AC: 90 AN: 1111798

Other (OTH) AF: 0.00901 AC: 544 AN: 60362

GnomAD4 genome AF: 0.00851 AC: 1296 AN: 152292 Hom.: 72 Cov.: 35 AF XY: 0.00928 AC XY: 691 AN XY: 74460

African (AFR) AF: 0.00149 AC: 62 AN: 41566

American (AMR) AF: 0.0255 AC: 391 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.152 AC: 787 AN: 5176

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68018

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Alfa AF: 0.00157 Hom.: 4

Bravo AF: 0.0124

Asia WGS AF: 0.0580 AC: 203 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Feb 20, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Sep 18, 2018

GeneDx

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Oct 20, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Connective tissue disorder Benign:1

May 26, 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.2
DANN	Benign	0.82
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00024
dbscSNV1_RF	Benign	0.018
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

Other links and lift over

dbSNP: rs74506912; hg19: chr20-61460107; COSMIC: COSV59651207; COSMIC: COSV59651207;