rs149690829

Positions:

• chr20-62821204-G-A
• chr20-62821204-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2 BP4_Strong BP6_Very_Strong BP7 BS1

The NM_001853.4(COL9A3):​c.333G>A​(p.Pro111Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000353 in 1,613,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00036 (0 hom.)
• Consequence: COL9A3 NM_001853.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.30

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-62821204-G-A is Benign according to our data. Variant chr20-62821204-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 198138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.3 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000263 (40/152280) while in subpopulation SAS AF= 0.00104 (5/4830). AF 95% confidence interval is 0.000408. There are 0 homozygotes in gnomad4. There are 22 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL9A3	NM_001853.4	c.333G>A	p.Pro111Pro	synonymous_variant	6/32	ENST00000649368.1	NP_001844.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL9A3	ENST00000649368.1	c.333G>A	p.Pro111Pro	synonymous_variant	6/32		NM_001853.4	ENSP00000496793.1
COL9A3	ENST00000452372.2	c.222G>A	p.Pro74Pro	synonymous_variant	5/12	5		ENSP00000394280.1
COL9A3	ENST00000477612.5	n.329G>A		non_coding_transcript_exon_variant	6/12	3
COL9A3	ENST00000489045.5	n.379G>A		non_coding_transcript_exon_variant	5/14	5

Frequencies

GnomAD3 genomes AF: 0.000263 AC: 40 AN: 152162 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00169

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000421 AC: 103 AN: 244630 Hom.: 0 AF XY: 0.000383 AC XY: 51 AN XY: 133138

Gnomad AFR exome AF: 0.0000634

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000164

Gnomad SAS exome AF: 0.000852

Gnomad FIN exome AF: 0.00154

Gnomad NFE exome AF: 0.000367

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000363 AC: 530 AN: 1460894 Hom.: 0 Cov.: 32 AF XY: 0.000361 AC XY: 262 AN XY: 726710

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000801

Gnomad4 FIN exome AF: 0.00219

Gnomad4 NFE exome AF: 0.000296

Gnomad4 OTH exome AF: 0.000199

GnomAD4 genome AF: 0.000263 AC: 40 AN: 152280 Hom.: 0 Cov.: 33 AF XY: 0.000296 AC XY: 22 AN XY: 74446

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00169

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000200 Hom.: 0

Bravo AF: 0.000121

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 30, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 27, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2024	COL9A3: BP4, BP7 -

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 06, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.49
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs149690829; hg19: chr20-61452556;