rs377557569

chr20-62819308-C-CCCT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001853.4(COL9A3):c.255+18_255+20dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00176 in 1,599,436 control chromosomes in the GnomAD database, including 56 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0094 (27 hom., cov: 33)
  • Exomes 𝑓: 0.00096 (29 hom.)
• Consequence: COL9A3 NM_001853.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0780

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 -16 ACMG points.

• BP6: Variant 20-62819308-C-CCCT is Benign according to our data. Variant chr20-62819308-C-CCCT is described in ClinVar as [Likely_benign]. Clinvar id is 258421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00939 (1430/152304) while in subpopulation AFR AF= 0.033 (1374/41574). AF 95% confidence interval is 0.0316. There are 27 homozygotes in gnomad4. There are 681 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A3	NM_001853.4	c.255+18_255+20dup		intron_variant		ENST00000649368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL9A3	ENST00000649368.1	c.255+18_255+20dup		intron_variant			NM_001853.4	P1
COL9A3	ENST00000452372.2	c.144+18_144+20dup		intron_variant		5
COL9A3	ENST00000477612.5	n.251+18_251+20dup		intron_variant, non_coding_transcript_variant		3
COL9A3	ENST00000489045.5	n.301+18_301+20dup		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00937 AC: 1426 AN: 152186 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.0331

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.00224 AC: 506 AN: 225648 Hom.: 10 AF XY: 0.00167 AC XY: 206 AN XY: 123018

Gnomad AFR exome AF: 0.0328

Gnomad AMR exome AF: 0.00117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000104

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000608

Gnomad OTH exome AF: 0.00109

GnomAD4 exome AF: 0.000960 AC: 1389 AN: 1447132 Hom.: 29 Cov.: 32 AF XY: 0.000841 AC XY: 605 AN XY: 719072

Gnomad4 AFR exome AF: 0.0345

Gnomad4 AMR exome AF: 0.00141

Gnomad4 ASJ exome AF: 0.0000388

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000707

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000389

Gnomad4 OTH exome AF: 0.00206

GnomAD4 genome AF: 0.00939 AC: 1430 AN: 152304 Hom.: 27 Cov.: 33 AF XY: 0.00914 AC XY: 681 AN XY: 74488

Gnomad4 AFR AF: 0.0330

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00534 Hom.: 3

Bravo AF: 0.0109

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs377557569; hg19: chr20-61450660;