rs149690829

Variant names:

• chr20-62821204-G-A
• rs149690829
• NM_001853.4:c.333G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-62821204-G-A
• chr20-62821204-G-C
• 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]

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 rank	MANE	Protein	UniProt
COL9A3	NM_001853.4	c.333G>A	p.Pro111Pro	synonymous_variant	Exon 6 of 32	ENST00000649368.1	NP_001844.3

Ensembl

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

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

COL9A3: BP4, BP7 -

Nov 30, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 06, 2017

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;