Variant 20-62817090-CGCTCCT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM4BS1_Supporting

The NM_001853.4(COL9A3):c.43_48delCTGCTC(p.Leu15_Leu16del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000563 in 1,242,384 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

COL9A3
NM_001853.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.123

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_001853.4.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000563 (70/1242384) while in subpopulation MID AF= 0.00115 (4/3474). AF 95% confidence interval is 0.000393. There are 0 homozygotes in gnomad4_exome. There are 43 alleles in male gnomad4_exome subpopulation. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A3	NM_001853.4 link	c.43_48delCTGCTC	p.Leu15_Leu16del	conservative_inframe_deletion	Exon 1 of 32	ENST00000649368.1	NP_001844.3	Q14050

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A3	ENST00000649368.1 link	c.43_48delCTGCTC	p.Leu15_Leu16del	conservative_inframe_deletion	Exon 1 of 32		NM_001853.4	ENSP00000496793.1		Q14050
COL9A3	ENST00000477612.5 link	n.75-460_75-455delCTGCTC		intron_variant	Intron 1 of 11	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000123

AC:

AN:

81068

Hom.:

AF XY:

0.0000213

AC XY:

AN XY:

46948

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000670

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000563

AC:

AN:

1242384

Hom.:

AF XY:

0.0000702

AC XY:

AN XY:

612634

show subpopulations

Gnomad4 AFR exome

AF:

0.0000400

Gnomad4 AMR exome

AF:

0.000289

Gnomad4 ASJ exome

AF:

0.0000988

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000183

Gnomad4 FIN exome

AF:

0.000134

Gnomad4 NFE exome

AF:

0.0000340

Gnomad4 OTH exome

AF:

0.000121

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 30, 2024

This variant, c.43_48del, results in the deletion of 2 amino acid(s) of the COL9A3 protein (p.Leu15_Leu16del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with COL9A3-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over