20-62828986-C-T

Position:

• chr20-62828986-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 258402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62828986-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL9A3	NM_001853.4	c.1008+10C>T		intron_variant		ENST00000649368.1	NP_001844.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL9A3	ENST00000649368.1	c.1008+10C>T		intron_variant			NM_001853.4	ENSP00000496793	P1
COL9A3	ENST00000463487.2			downstream_gene_variant		5

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

GnomAD3 exomes AF: 0.527 AC: 116053 AN: 220066 Hom.: 31494 AF XY: 0.519 AC XY: 62815 AN XY: 120944

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 SAS exome AF: 0.543

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

Gnomad4 AFR exome AF: 0.808

Gnomad4 AMR exome AF: 0.543

Gnomad4 ASJ exome AF: 0.453

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 0.535

Gnomad4 FIN exome AF: 0.465

Gnomad4 NFE exome AF: 0.443

Gnomad4 OTH exome AF: 0.498

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

Gnomad4 AFR AF: 0.790

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.466

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.548

Alfa AF: 0.484 Hom.: 3318

Bravo AF: 0.575

Asia WGS AF: 0.653 AC: 2270 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2017	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. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Epiphyseal dysplasia, multiple, 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.067
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs6062700; hg19: chr20-61460338;