Variant chr20-63295180-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020882.4(COL20A1):c.73C>G(p.Gln25Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,553,252 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 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

COL20A1
NM_020882.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.961

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]

COL20A1 links:

COL20A1 (HGNC:):

COL20A1 links:

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=0.11275843).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL20A1	NM_020882.4 linkuse as main transcript	c.73C>G	p.Gln25Glu	missense_variant	2/36	ENST00000358894.11	NP_065933.2	Q9P218-1
COL20A1	XM_011528937.2 linkuse as main transcript	c.73C>G	p.Gln25Glu	missense_variant	2/36		XP_011527239.1
COL20A1	XM_011528938.2 linkuse as main transcript	c.73C>G	p.Gln25Glu	missense_variant	2/36		XP_011527240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
COL20A1	ENST00000358894.11 linkuse as main transcript	c.73C>G	p.Gln25Glu	missense_variant	2/36	1	NM_020882.4	ENSP00000351767.6	Q9P218-1
COL20A1	ENST00000479501.5 linkuse as main transcript	n.135C>G		non_coding_transcript_exon_variant	2/36	1
COL20A1	ENST00000422202.5 linkuse as main transcript	c.73C>G	p.Gln25Glu	missense_variant	1/35	5		ENSP00000414753.1	Q9P218-2

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000891

AC:

AN:

157188

Hom.:

AF XY:

0.0000835

AC XY:

AN XY:

83812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000120

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000138

AC:

194

AN:

1400868

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

691420

show subpopulations

Gnomad4 AFR exome

AF:

0.0000315

Gnomad4 AMR exome

AF:

0.000249

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000162

Gnomad4 OTH exome

AF:

0.000138

GnomAD4 genome

AF:

0.0000656

AC:

AN:

152384

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000326

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000993

Hom.:

Bravo

AF:

0.000181

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000246

AC:

ExAC

AF:

0.0000285

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 27, 2023

The c.73C>G (p.Q25E) alteration is located in exon 2 (coding exon 1) of the COL20A1 gene. This alteration results from a C to G substitution at nucleotide position 73, causing the glutamine (Q) at amino acid position 25 to be replaced by a glutamic acid (E). 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

0.069

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.65

DEOGEN2

Benign

0.0082

T;.

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.068

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.84

N;N

REVEL

Benign

0.20

Sift

Benign

0.19

T;T

Sift4G

Uncertain

0.011

D;T

Polyphen

0.0030

B;.

Vest4

0.23

MVP

0.82

MPC

0.057

ClinPred

0.028

GERP RS

2.8

Varity_R

0.17

gMVP

0.014

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over