20-63307491-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The ENST00000358894.11(COL20A1):​c.498C>T​(p.Ala166=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000358 in 1,610,752 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00036 ( 3 hom. )

Consequence

COL20A1
ENST00000358894.11 splice_region, synonymous

Scores

2
Splicing: ADA: 0.00001184
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.101
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 Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP7
Synonymous conserved (PhyloP=-0.101 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COL20A1NM_020882.4 linkuse as main transcriptc.498C>T p.Ala166= splice_region_variant, synonymous_variant 6/36 ENST00000358894.11 NP_065933.2
COL20A1XM_011528937.2 linkuse as main transcriptc.498C>T p.Ala166= splice_region_variant, synonymous_variant 6/36 XP_011527239.1
COL20A1XM_011528938.2 linkuse as main transcriptc.498C>T p.Ala166= splice_region_variant, synonymous_variant 6/36 XP_011527240.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COL20A1ENST00000358894.11 linkuse as main transcriptc.498C>T p.Ala166= splice_region_variant, synonymous_variant 6/361 NM_020882.4 ENSP00000351767 P2Q9P218-1
COL20A1ENST00000479501.5 linkuse as main transcriptn.560C>T splice_region_variant, non_coding_transcript_exon_variant 6/361
COL20A1ENST00000422202.5 linkuse as main transcriptc.519C>T p.Thr173= splice_region_variant, synonymous_variant 5/355 ENSP00000414753 A2Q9P218-2

Frequencies

GnomAD3 genomes
AF:
0.000361
AC:
55
AN:
152204
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000471
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.000449
AC:
110
AN:
244806
Hom.:
1
AF XY:
0.000516
AC XY:
69
AN XY:
133618
show subpopulations
Gnomad AFR exome
AF:
0.000332
Gnomad AMR exome
AF:
0.0000583
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00207
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000326
Gnomad OTH exome
AF:
0.000674
GnomAD4 exome
AF:
0.000358
AC:
522
AN:
1458430
Hom.:
3
Cov.:
32
AF XY:
0.000398
AC XY:
289
AN XY:
725544
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.0000672
Gnomad4 ASJ exome
AF:
0.0000384
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.00159
Gnomad4 FIN exome
AF:
0.0000388
Gnomad4 NFE exome
AF:
0.000302
Gnomad4 OTH exome
AF:
0.000481
GnomAD4 genome
AF:
0.000361
AC:
55
AN:
152322
Hom.:
0
Cov.:
33
AF XY:
0.000376
AC XY:
28
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.000240
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000471
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.000144
Hom.:
0
Bravo
AF:
0.000268
EpiCase
AF:
0.000545
EpiControl
AF:
0.000475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
1.6
DANN
Benign
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000012
dbscSNV1_RF
Benign
0.0
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: rs3746373; hg19: chr20-61938843; API