20-62826200-G-T

Variant names:

• chr20-62826200-G-T
• rs57739618
• NM_001853.4:c.685-4G>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.685-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00473 in 1,559,510 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (140 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (111 hom.)
• Consequence: COL9A3 NM_001853.4 splice_region, intron
• Scores: Splicing: ADA: 0.00005329
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -3.82

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=-0.91).
• BP6: Variant 20-62826200-G-T is Benign according to our data. Variant chr20-62826200-G-T is described in ClinVar as [Benign]. Clinvar id is 258430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62826200-G-T is described in Lovd as [Likely_benign]. Variant chr20-62826200-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A3	NM_001853.4	c.685-4G>T		splice_region_variant, intron_variant	Intron 13 of 31	ENST00000649368.1	NP_001844.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A3	ENST00000649368.1	c.685-4G>T		splice_region_variant, intron_variant	Intron 13 of 31		NM_001853.4	ENSP00000496793.1
COL9A3	ENST00000463487.2	n.393-4G>T		splice_region_variant, intron_variant	Intron 5 of 10	5
COL9A3	ENST00000489045.5	n.731-4G>T		splice_region_variant, intron_variant	Intron 12 of 13	5

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3488 AN: 152100 Hom.: 139 Cov.: 33

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00791

Gnomad ASJ AF: 0.00837

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000574

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.00627 AC: 1049 AN: 167238 Hom.: 31 AF XY: 0.00449 AC XY: 401 AN XY: 89276

Gnomad AFR exome AF: 0.0789

Gnomad AMR exome AF: 0.00597

Gnomad ASJ exome AF: 0.00711

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000253

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000468

Gnomad OTH exome AF: 0.00500

GnomAD4 exome AF: 0.00275 AC: 3877 AN: 1407292 Hom.: 111 Cov.: 33 AF XY: 0.00241 AC XY: 1679 AN XY: 695362

Gnomad4 AFR exome AF: 0.0832

Gnomad4 AMR exome AF: 0.00626

Gnomad4 ASJ exome AF: 0.00690

Gnomad4 EAS exome AF: 0.0000272

Gnomad4 SAS exome AF: 0.000338

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000349

Gnomad4 OTH exome AF: 0.00619

GnomAD4 genome AF: 0.0230 AC: 3498 AN: 152218 Hom.: 140 Cov.: 33 AF XY: 0.0218 AC XY: 1622 AN XY: 74422

Gnomad4 AFR AF: 0.0787

Gnomad4 AMR AF: 0.00790

Gnomad4 ASJ AF: 0.00837

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000559

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00262 Hom.: 1

Bravo AF: 0.0266

Asia WGS AF: 0.00520 AC: 19 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Sep 16, 2024

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 09, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:4

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: 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	0.038
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000053
dbscSNV1_RF	Benign	0.0
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: rs57739618; hg19: chr20-61457552;