rs2273078

Positions:

• chr20-62817581-C-A
• chr20-62817581-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001853.4(COL9A3):​c.93C>A​(p.Pro31=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0811 in 1,539,566 control chromosomes in the GnomAD database, including 6,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1252 hom., cov: 33)
  • Exomes 𝑓: 0.077 (5421 hom.)
• Consequence: COL9A3 NM_001853.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.0150

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 20-62817581-C-A is Benign according to our data. Variant chr20-62817581-C-A is described in ClinVar as [Benign]. Clinvar id is 195154.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62817581-C-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.015 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A3	NM_001853.4	c.93C>A	p.Pro31=	synonymous_variant	2/32	ENST00000649368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A3	ENST00000649368.1	c.93C>A	p.Pro31=	synonymous_variant	2/32		NM_001853.4	P1
COL9A3	ENST00000477612.5	n.89C>A		non_coding_transcript_exon_variant	2/12	3
COL9A3	ENST00000489045.5	n.139C>A		non_coding_transcript_exon_variant	1/14	5

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17559 AN: 151698 Hom.: 1248 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.0940

Gnomad FIN AF: 0.0895

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0664

Gnomad OTH AF: 0.130

GnomAD3 exomes AF: 0.110 AC: 15857 AN: 143678 Hom.: 1140 AF XY: 0.106 AC XY: 8181 AN XY: 77530

Gnomad AFR exome AF: 0.191

Gnomad AMR exome AF: 0.140

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.282

Gnomad SAS exome AF: 0.0859

Gnomad FIN exome AF: 0.0843

Gnomad NFE exome AF: 0.0683

Gnomad OTH exome AF: 0.100

GnomAD4 exome AF: 0.0773 AC: 107298 AN: 1387750 Hom.: 5421 Cov.: 30 AF XY: 0.0774 AC XY: 52982 AN XY: 684142

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.270

Gnomad4 SAS exome AF: 0.0900

Gnomad4 FIN exome AF: 0.0810

Gnomad4 NFE exome AF: 0.0628

Gnomad4 OTH exome AF: 0.0951

GnomAD4 genome AF: 0.116 AC: 17601 AN: 151816 Hom.: 1252 Cov.: 33 AF XY: 0.117 AC XY: 8709 AN XY: 74184

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.0941

Gnomad4 FIN AF: 0.0895

Gnomad4 NFE AF: 0.0664

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0813 Hom.: 229

Bravo AF: 0.125

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 30, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 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:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

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	-0.66
CADD	Benign	2.9
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2273078; hg19: chr20-61448933; COSMIC: COSV51699160; COSMIC: COSV51699160;