NM_001853.4:c.1476C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001853.4(COL9A3):​c.1476C>T​(p.Pro492Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00206 in 1,613,766 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0071 ( 15 hom., cov: 34)
Exomes 𝑓: 0.0015 ( 27 hom. )

Consequence

COL9A3
NM_001853.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -3.36
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 20-62836261-C-T is Benign according to our data. Variant chr20-62836261-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 258410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.36 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00715 (1089/152360) while in subpopulation AFR AF= 0.0238 (988/41592). AF 95% confidence interval is 0.0225. There are 15 homozygotes in gnomad4. There are 529 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL9A3NM_001853.4 linkc.1476C>T p.Pro492Pro synonymous_variant Exon 28 of 32 ENST00000649368.1 NP_001844.3 Q14050

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL9A3ENST00000649368.1 linkc.1476C>T p.Pro492Pro synonymous_variant Exon 28 of 32 NM_001853.4 ENSP00000496793.1 Q14050

Frequencies

GnomAD3 genomes
AF:
0.00713
AC:
1085
AN:
152242
Hom.:
15
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0237
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00196
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0122
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00431
GnomAD3 exomes
AF:
0.00332
AC:
825
AN:
248702
Hom.:
8
AF XY:
0.00344
AC XY:
465
AN XY:
135290
show subpopulations
Gnomad AFR exome
AF:
0.0254
Gnomad AMR exome
AF:
0.00104
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0124
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000980
Gnomad OTH exome
AF:
0.00148
GnomAD4 exome
AF:
0.00153
AC:
2242
AN:
1461406
Hom.:
27
Cov.:
33
AF XY:
0.00179
AC XY:
1302
AN XY:
727022
show subpopulations
Gnomad4 AFR exome
AF:
0.0256
Gnomad4 AMR exome
AF:
0.00114
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0120
Gnomad4 FIN exome
AF:
0.0000189
Gnomad4 NFE exome
AF:
0.000130
Gnomad4 OTH exome
AF:
0.00245
GnomAD4 genome
AF:
0.00715
AC:
1089
AN:
152360
Hom.:
15
Cov.:
34
AF XY:
0.00710
AC XY:
529
AN XY:
74508
show subpopulations
Gnomad4 AFR
AF:
0.0238
Gnomad4 AMR
AF:
0.00196
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.0122
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00378
Hom.:
1
Bravo
AF:
0.00814
Asia WGS
AF:
0.00751
AC:
26
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000296

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:4
Nov 14, 2018
Athena Diagnostics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Feb 01, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Nov 24, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Connective tissue disorder Benign:1
Mar 01, 2020
Genome Diagnostics Laboratory, The Hospital for Sick Children
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.20
DANN
Benign
0.85
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs76559905; hg19: chr20-61467613; API