rs74830351

Variant names:

• chr20-62840573-C-G
• NM_001853.4:c.1896C>G

Your query was ambiguous. Multiple possible variants found:

• chr20-62840573-C-G
• chr20-62840573-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001853.4(COL9A3):​c.1896C>G​(p.Asp632Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,264 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D632D) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: COL9A3 NM_001853.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL9A3	NM_001853.4	c.1896C>G	p.Asp632Glu	missense_variant	Exon 32 of 32	ENST00000649368.1	NP_001844.3
COL9A3	XM_047439893.1	c.2073C>G	p.Asp691Glu	missense_variant	Exon 31 of 31		XP_047295849.1
COL9A3	XM_047439894.1	c.1335C>G	p.Asp445Glu	missense_variant	Exon 32 of 32		XP_047295850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL9A3	ENST00000649368.1	c.1896C>G	p.Asp632Glu	missense_variant	Exon 32 of 32		NM_001853.4	ENSP00000496793.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460264 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726496

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	0.0067	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	0.20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0047	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.64	.;T
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Uncertain	0.077	D
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.4	.;N
REVEL	Uncertain	0.42
Sift	Benign	0.052	.;T
Sift4G	Benign	0.38	.;T
Polyphen		1.0	D;D
Vest4		0.30
MutPred		0.22		Gain of solvent accessibility (P = 0.0854);Gain of solvent accessibility (P = 0.0854);
MVP		0.56
MPC		0.41
ClinPred		0.94	D
GERP RS		-4.5
Varity_R		0.17
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-61471925;