20-62836178-C-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.1402-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0071 in 1,612,930 control chromosomes in the GnomAD database, including 514 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (255 hom., cov: 34)
  • Exomes 𝑓: 0.0045 (259 hom.)
• Consequence: COL9A3 NM_001853.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001526
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0840

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=-0.75).
• BP6: Variant 20-62836178-C-T is Benign according to our data. Variant chr20-62836178-C-T is described in ClinVar as [Benign]. Clinvar id is 258408.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-62836178-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A3	NM_001853.4	c.1402-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000649368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A3	ENST00000649368.1	c.1402-9C>T		splice_polypyrimidine_tract_variant, intron_variant			NM_001853.4	P1

Frequencies

GnomAD3 genomes AF: 0.0316 AC: 4805 AN: 152232 Hom.: 254 Cov.: 34

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0158

Gnomad ASJ AF: 0.00835

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000558

Gnomad OTH AF: 0.0220

GnomAD3 exomes AF: 0.0102 AC: 2512 AN: 245770 Hom.: 110 AF XY: 0.00903 AC XY: 1211 AN XY: 134088

Gnomad AFR exome AF: 0.115

Gnomad AMR exome AF: 0.00692

Gnomad ASJ exome AF: 0.00655

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.0128

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000553

Gnomad OTH exome AF: 0.00652

GnomAD4 exome AF: 0.00454 AC: 6638 AN: 1460580 Hom.: 259 Cov.: 33 AF XY: 0.00444 AC XY: 3223 AN XY: 726554

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.00790

Gnomad4 ASJ exome AF: 0.00678

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000486

Gnomad4 OTH exome AF: 0.00970

GnomAD4 genome AF: 0.0316 AC: 4818 AN: 152350 Hom.: 255 Cov.: 34 AF XY: 0.0309 AC XY: 2304 AN XY: 74510

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0158

Gnomad4 ASJ AF: 0.00835

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0137

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000558

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0152 Hom.: 43

Bravo AF: 0.0371

Asia WGS AF: 0.0160 AC: 55 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000950

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 01, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Connective tissue disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Feb 04, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	7.9
Dann	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000015
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: rs57754593; hg19: chr20-61467530;