chr20-62833023-A-G

Position:

• chr20-62833023-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001853.4(COL9A3):​c.1327A>G​(p.Ile443Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,613,604 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0095 (27 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (16 hom.)
• Consequence: COL9A3 NM_001853.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.26

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 (MetaRNN=0.0038558543).
• BP6: Variant 20-62833023-A-G is Benign according to our data. Variant chr20-62833023-A-G is described in ClinVar as [Benign]. Clinvar id is 258405.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 = 0.00951 (1449/152298) while in subpopulation AFR AF= 0.0309 (1283/41550). AF 95% confidence interval is 0.0295. There are 27 homozygotes in gnomad4. There are 689 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL9A3	NM_001853.4	c.1327A>G	p.Ile443Val	missense_variant	26/32	ENST00000649368.1	NP_001844.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL9A3	ENST00000649368.1	c.1327A>G	p.Ile443Val	missense_variant	26/32		NM_001853.4	ENSP00000496793	P1

Frequencies

GnomAD3 genomes AF: 0.00949 AC: 1444 AN: 152180 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.0308

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00766

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00262 AC: 659 AN: 251102 Hom.: 8 AF XY: 0.00213 AC XY: 289 AN XY: 135864

Gnomad AFR exome AF: 0.0320

Gnomad AMR exome AF: 0.00237

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000361

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00111 AC: 1620 AN: 1461306 Hom.: 16 Cov.: 30 AF XY: 0.00101 AC XY: 736 AN XY: 726988

Gnomad4 AFR exome AF: 0.0291

Gnomad4 AMR exome AF: 0.00309

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000273

Gnomad4 OTH exome AF: 0.00287

GnomAD4 genome AF: 0.00951 AC: 1449 AN: 152298 Hom.: 27 Cov.: 33 AF XY: 0.00925 AC XY: 689 AN XY: 74470

Gnomad4 AFR AF: 0.0309

Gnomad4 AMR AF: 0.00765

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.00993

Alfa AF: 0.00232 Hom.: 7

Bravo AF: 0.0111

ESP6500AA AF: 0.0304 AC: 134

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00334 AC: 405

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 19, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	0.61
DANN	Benign	0.69
DEOGEN2	Benign	0.00043	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.67	.;T
MetaRNN	Benign	0.0039	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.48	N;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.16	.;N
REVEL	Benign	0.21
Sift	Benign	0.80	.;T
Sift4G	Benign	0.32	.;T
Polyphen		0.0050	B;B
Vest4		0.23
MVP		0.55
MPC		0.086
ClinPred		0.00088	T
GERP RS		-1.8
Varity_R		0.026
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs79269394; hg19: chr20-61464375;