Variant 20-63307997-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000358894.11(COL20A1):c.682C>G(p.Gln228Glu) 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 1,612,474 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 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

COL20A1
ENST00000358894.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.231

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27582484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
COL20A1	NM_020882.4 linkuse as main transcript	c.682C>G	p.Gln228Glu	missense_variant	7/36	ENST00000358894.11	NP_065933.2
COL20A1	XM_011528937.2 linkuse as main transcript	c.682C>G	p.Gln228Glu	missense_variant	7/36		XP_011527239.1
COL20A1	XM_011528938.2 linkuse as main transcript	c.682C>G	p.Gln228Glu	missense_variant	7/36		XP_011527240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL20A1	ENST00000358894.11 linkuse as main transcript	c.682C>G	p.Gln228Glu	missense_variant	7/36	1	NM_020882.4	ENSP00000351767	P2	Q9P218-1
COL20A1	ENST00000479501.5 linkuse as main transcript	n.744C>G		non_coding_transcript_exon_variant	7/36	1
COL20A1	ENST00000422202.5 linkuse as main transcript	c.703C>G	p.Gln235Glu	missense_variant	6/35	5		ENSP00000414753	A2	Q9P218-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000322

AC:

AN:

1460316

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

AN XY:

726446

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000387

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74332

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Mar 22, 2023

The c.682C>G (p.Q228E) alteration is located in exon 7 (coding exon 6) of the COL20A1 gene. This alteration results from a C to G substitution at nucleotide position 682, causing the glutamine (Q) at amino acid position 228 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

0.081

BayesDel_addAF

Benign

-0.035

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.051

T;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.24

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.061

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

0.99

N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.28

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.48

P;B

Vest4

0.40

MutPred

0.53

Gain of disorder (P = 0.0812);.;

MVP

0.84

MPC

0.12

ClinPred

0.50

GERP RS

3.1

Varity_R

0.34

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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