chr20-62836546-G-C

Position:

• chr20-62836546-G-C

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.1603+14G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 1,603,554 control chromosomes in the GnomAD database, including 653,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (63991 hom., cov: 34)
  • Exomes 𝑓: 0.90 (589022 hom.)
• Consequence: COL9A3 NM_001853.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -0.929

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=-0.95).
• BP6: Variant 20-62836546-G-C is Benign according to our data. Variant chr20-62836546-G-C is described in ClinVar as [Benign]. Clinvar id is 258415.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62836546-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL9A3	NM_001853.4	c.1603+14G>C		intron_variant		ENST00000649368.1	NP_001844.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL9A3	ENST00000649368.1	c.1603+14G>C		intron_variant			NM_001853.4	ENSP00000496793	P1

Frequencies

GnomAD3 genomes AF: 0.916 AC: 139389 AN: 152126 Hom.: 63940 Cov.: 34

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.921

Gnomad AMR AF: 0.910

Gnomad ASJ AF: 0.949

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.954

Gnomad FIN AF: 0.930

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.896

GnomAD3 exomes AF: 0.920 AC: 212212 AN: 230572 Hom.: 97728 AF XY: 0.920 AC XY: 115206 AN XY: 125272

Gnomad AFR exome AF: 0.944

Gnomad AMR exome AF: 0.946

Gnomad ASJ exome AF: 0.950

Gnomad EAS exome AF: 0.943

Gnomad SAS exome AF: 0.954

Gnomad FIN exome AF: 0.924

Gnomad NFE exome AF: 0.893

Gnomad OTH exome AF: 0.906

GnomAD4 exome AF: 0.900 AC: 1306898 AN: 1451310 Hom.: 589022 Cov.: 47 AF XY: 0.902 AC XY: 650030 AN XY: 720812

Gnomad4 AFR exome AF: 0.945

Gnomad4 AMR exome AF: 0.942

Gnomad4 ASJ exome AF: 0.945

Gnomad4 EAS exome AF: 0.955

Gnomad4 SAS exome AF: 0.954

Gnomad4 FIN exome AF: 0.925

Gnomad4 NFE exome AF: 0.889

Gnomad4 OTH exome AF: 0.907

GnomAD4 genome AF: 0.916 AC: 139500 AN: 152244 Hom.: 63991 Cov.: 34 AF XY: 0.919 AC XY: 68362 AN XY: 74416

Gnomad4 AFR AF: 0.943

Gnomad4 AMR AF: 0.910

Gnomad4 ASJ AF: 0.949

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.954

Gnomad4 FIN AF: 0.930

Gnomad4 NFE AF: 0.893

Gnomad4 OTH AF: 0.897

Alfa AF: 0.905 Hom.: 6785

Bravo AF: 0.916

Asia WGS AF: 0.953 AC: 3311 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:7

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus 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	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 08, 2015	- -

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	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.56
DANN	Benign	0.24

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: rs910152; hg19: chr20-61467898;