rs188924459

chr20-62827907-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_001853.4(COL9A3):c.847-16C>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 0.000649 in 1,612,904 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00073 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00064 (6 hom.)
• Consequence: COL9A3 NM_001853.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.183

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 20-62827907-C-T is Benign according to our data. Variant chr20-62827907-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 258435.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000729 (111/152366) while in subpopulation AMR AF= 0.000784 (12/15302). AF 95% confidence interval is 0.000452. There are 1 homozygotes in gnomad4. There are 48 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL9A3	NM_001853.4	c.847-16C>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.847-16C>T		splice_polypyrimidine_tract_variant, intron_variant			NM_001853.4	P1
COL9A3	ENST00000463487.2	n.555-16C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.000723 AC: 110 AN: 152248 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00104 AC: 261 AN: 250254 Hom.: 1 AF XY: 0.000958 AC XY: 130 AN XY: 135666

Gnomad AFR exome AF: 0.0000619

Gnomad AMR exome AF: 0.000492

Gnomad ASJ exome AF: 0.0162

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000558

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.000640 AC: 935 AN: 1460538 Hom.: 6 Cov.: 31 AF XY: 0.000629 AC XY: 457 AN XY: 726556

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.000514

Gnomad4 ASJ exome AF: 0.0141

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000263

Gnomad4 OTH exome AF: 0.00230

GnomAD4 genome AF: 0.000729 AC: 111 AN: 152366 Hom.: 1 Cov.: 33 AF XY: 0.000644 AC XY: 48 AN XY: 74508

Gnomad4 AFR AF: 0.000144

Gnomad4 AMR AF: 0.000784

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00293 Hom.: 2

Bravo AF: 0.000752

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	11
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs188924459; hg19: chr20-61459259;