20-63306030-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020882.4(COL20A1):​c.487C>T​(p.Arg163Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,610,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

COL20A1
NM_020882.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.901
Variant links:
Genes affected
COL20A1 (HGNC:14670): (collagen type XX alpha 1 chain) Predicted to be located in endoplasmic reticulum lumen and extracellular region. Predicted to be part of collagen trimer. Predicted to be active in collagen-containing extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13532451).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COL20A1NM_020882.4 linkc.487C>T p.Arg163Cys missense_variant Exon 5 of 36 ENST00000358894.11 NP_065933.2 Q9P218-1
COL20A1XM_011528937.2 linkc.487C>T p.Arg163Cys missense_variant Exon 5 of 36 XP_011527239.1
COL20A1XM_011528938.2 linkc.487C>T p.Arg163Cys missense_variant Exon 5 of 36 XP_011527240.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COL20A1ENST00000358894.11 linkc.487C>T p.Arg163Cys missense_variant Exon 5 of 36 1 NM_020882.4 ENSP00000351767.6 Q9P218-1
COL20A1ENST00000479501.5 linkn.549C>T non_coding_transcript_exon_variant Exon 5 of 36 1
COL20A1ENST00000422202.5 linkc.487C>T p.Arg163Cys missense_variant Exon 4 of 35 5 ENSP00000414753.1 Q9P218-2

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152254
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000408
AC:
10
AN:
245194
Hom.:
0
AF XY:
0.0000375
AC XY:
5
AN XY:
133248
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000118
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000112
Gnomad SAS exome
AF:
0.0000333
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000271
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000309
AC:
45
AN:
1458026
Hom.:
0
Cov.:
32
AF XY:
0.0000317
AC XY:
23
AN XY:
725136
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000902
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000466
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000288
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152254
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000567
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000331
AC:
4
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.487C>T (p.R163C) alteration is located in exon 5 (coding exon 4) of the COL20A1 gene. This alteration results from a C to T substitution at nucleotide position 487, causing the arginine (R) at amino acid position 163 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
15
DANN
Benign
0.95
DEOGEN2
Benign
0.0039
T;.
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.71
FATHMM_MKL
Benign
0.24
N
LIST_S2
Benign
0.46
T;T
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-0.81
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.40
N;N
REVEL
Benign
0.15
Sift
Benign
0.12
T;D
Sift4G
Benign
0.087
T;T
Polyphen
0.14
B;.
Vest4
0.22
MutPred
0.22
Gain of catalytic residue at P162 (P = 0.0074);Gain of catalytic residue at P162 (P = 0.0074);
MVP
0.82
MPC
0.042
ClinPred
0.047
T
GERP RS
3.9
Varity_R
0.10
gMVP
0.17

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: rs768939773; hg19: chr20-61937382; API