20-62828986-C-T

Variant names:

• chr20-62828986-C-T
• rs6062700
• NM_001853.4:c.1008+10C>T

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.1008+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 1,596,078 control chromosomes in the GnomAD database, including 190,486 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (25685 hom., cov: 34)
  • Exomes 𝑓: 0.47 (164801 hom.)
• Consequence: COL9A3 NM_001853.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.75
• Publications: 10 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: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Stickler syndrome

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

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.9).
• BP6: Variant 20-62828986-C-T is Benign according to our data. Variant chr20-62828986-C-T is described in ClinVar as Benign. ClinVar VariationId is 258402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL9A3	NM_001853.4	MANE Select	c.1008+10C>T		intron	N/A	NP_001844.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL9A3	ENST00000649368.1	MANE Select	c.1008+10C>T		intron	N/A	ENSP00000496793.1	Q14050
	COL9A3	ENST00000934236.1		c.1059+10C>T		intron	N/A	ENSP00000604295.1
	COL9A3	ENST00000894732.1		c.936+10C>T		intron	N/A	ENSP00000564791.1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84996 AN: 152004 Hom.: 25621 Cov.: 34

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.542

GnomAD2 exomes AF: 0.527 AC: 116053 AN: 220066 AF XY: 0.519

Gnomad AFR exome AF: 0.807

Gnomad AMR exome AF: 0.548

Gnomad ASJ exome AF: 0.450

Gnomad EAS exome AF: 0.765

Gnomad FIN exome AF: 0.483

Gnomad NFE exome AF: 0.454

Gnomad OTH exome AF: 0.491

GnomAD4 exome AF: 0.471 AC: 680780 AN: 1443956 Hom.: 164801 Cov.: 49 AF XY: 0.472 AC XY: 338721 AN XY: 717432

African (AFR) AF: 0.808 AC: 26812 AN: 33178

American (AMR) AF: 0.543 AC: 23415 AN: 43124

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 11724 AN: 25880

East Asian (EAS) AF: 0.750 AC: 29281 AN: 39016

South Asian (SAS) AF: 0.535 AC: 45376 AN: 84764

European-Finnish (FIN) AF: 0.465 AC: 22563 AN: 48498

Middle Eastern (MID) AF: 0.539 AC: 2395 AN: 4440

European-Non Finnish (NFE) AF: 0.443 AC: 489500 AN: 1105442

Other (OTH) AF: 0.498 AC: 29714 AN: 59614

GnomAD4 genome AF: 0.560 AC: 85121 AN: 152122 Hom.: 25685 Cov.: 34 AF XY: 0.559 AC XY: 41542 AN XY: 74368

African (AFR) AF: 0.790 AC: 32805 AN: 41524

American (AMR) AF: 0.511 AC: 7820 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1616 AN: 3470

East Asian (EAS) AF: 0.755 AC: 3893 AN: 5156

South Asian (SAS) AF: 0.548 AC: 2645 AN: 4830

European-Finnish (FIN) AF: 0.467 AC: 4946 AN: 10584

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29795 AN: 67948

Other (OTH) AF: 0.548 AC: 1159 AN: 2114

Alfa AF: 0.484 Hom.: 3318

Bravo AF: 0.575

Asia WGS AF: 0.653 AC: 2270 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	not provided (2)
-	-	1	Epiphyseal dysplasia, multiple, 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.067
DANN	Benign	0.75
PhyloP100		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6062700; hg19: chr20-61460338;