rs1036479876

Variant names:

• chr20-62817090-CGCTCCTGCTCCT-C
• rs1036479876
• NM_001853.4:c.37_48delCTGCTCCTGCTC

Your query was ambiguous. Multiple possible variants found:

• chr20-62817090-CGCTCCTGCTCCT-C
• chr20-62817090-CGCTCCTGCTCCT-CGCTCCT
• chr20-62817090-CGCTCCTGCTCCT-CGCTCCTGCTCCTGCTCCT
• chr20-62817090-CGCTCCTGCTCCT-CGCTCCTGCTCCTGCTCCTGCTCCT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_001853.4(COL9A3):​c.37_48delCTGCTCCTGCTC​(p.Leu13_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 0.00000241 in 1,243,336 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L13L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: COL9A3 NM_001853.4 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.912
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• epiphyseal dysplasia, multiple, 3

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Stickler syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: ClinGen, Ambry Genetics, Genomics England PanelApp
• Stickler syndrome, type 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• multiple epiphyseal dysplasia due to collagen 9 anomaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive Stickler syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001853.4.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001853.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL9A3	NM_001853.4	MANE Select	c.37_48delCTGCTCCTGCTC	p.Leu13_Leu16del	conservative_inframe_deletion	Exon 1 of 32	NP_001844.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL9A3	ENST00000649368.1	MANE Select	c.37_48delCTGCTCCTGCTC	p.Leu13_Leu16del	conservative_inframe_deletion	Exon 1 of 32	ENSP00000496793.1	Q14050
	COL9A3	ENST00000934236.1		c.37_48delCTGCTCCTGCTC	p.Leu13_Leu16del	conservative_inframe_deletion	Exon 1 of 33	ENSP00000604295.1
	COL9A3	ENST00000894732.1		c.37_48delCTGCTCCTGCTC	p.Leu13_Leu16del	conservative_inframe_deletion	Exon 1 of 31	ENSP00000564791.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000241 AC: 3 AN: 1243336 Hom.: 0 AF XY: 0.00000163 AC XY: 1 AN XY: 613184

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25030

American (AMR) AF: 0.00 AC: 0 AN: 24230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20268

East Asian (EAS) AF: 0.00 AC: 0 AN: 24524

South Asian (SAS) AF: 0.0000152 AC: 1 AN: 65676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3484

European-Non Finnish (NFE) AF: 0.00000200 AC: 2 AN: 1000798

Other (OTH) AF: 0.00 AC: 0 AN: 49470

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.91

Splicing

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

Other links and lift over

dbSNP: rs1036479876; hg19: chr20-61448442;