Variant 20-63308559-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000358894.11(COL20A1):c.793G>A(p.Val265Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000798 in 1,603,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

COL20A1
ENST00000358894.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.45

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.819

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
COL20A1	NM_020882.4 linkuse as main transcript	c.793G>A	p.Val265Met	missense_variant	8/36	ENST00000358894.11	NP_065933.2
COL20A1	XM_011528937.2 linkuse as main transcript	c.793G>A	p.Val265Met	missense_variant	8/36		XP_011527239.1
COL20A1	XM_011528938.2 linkuse as main transcript	c.793G>A	p.Val265Met	missense_variant	8/36		XP_011527240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL20A1	ENST00000358894.11 linkuse as main transcript	c.793G>A	p.Val265Met	missense_variant	8/36	1	NM_020882.4	ENSP00000351767	P2	Q9P218-1
COL20A1	ENST00000479501.5 linkuse as main transcript	n.855G>A		non_coding_transcript_exon_variant	8/36	1
COL20A1	ENST00000422202.5 linkuse as main transcript	c.814G>A	p.Val272Met	missense_variant	7/35	5		ENSP00000414753	A2	Q9P218-2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000118

AC:

AN:

229478

Hom.:

AF XY:

0.000112

AC XY:

AN XY:

125486

show subpopulations

Gnomad AFR exome

AF:

0.0000762

Gnomad AMR exome

AF:

0.000121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000117

Gnomad SAS exome

AF:

0.000105

Gnomad FIN exome

AF:

0.0000993

Gnomad NFE exome

AF:

0.000136

Gnomad OTH exome

AF:

0.000176

GnomAD4 exome

AF:

0.0000772

AC:

112

AN:

1450858

Hom.:

Cov.:

AF XY:

0.0000888

AC XY:

AN XY:

720838

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.000138

Gnomad4 ASJ exome

AF:

0.0000389

Gnomad4 EAS exome

AF:

0.0000763

Gnomad4 SAS exome

AF:

0.0000592

Gnomad4 FIN exome

AF:

0.000156

Gnomad4 NFE exome

AF:

0.0000686

Gnomad4 OTH exome

AF:

0.000167

GnomAD4 genome

AF:

0.000105

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.000125

AC:

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

Jan 05, 2022

The c.793G>A (p.V265M) alteration is located in exon 8 (coding exon 7) of the COL20A1 gene. This alteration results from a G to A substitution at nucleotide position 793, causing the valine (V) at amino acid position 265 to be replaced by a methionine (M). 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

Uncertain

0.39

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.89

D;D

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Uncertain

0.37

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

0.98

D;D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-2.2

N;N

REVEL

Uncertain

0.59

Sift

Uncertain

0.0030

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.61

MutPred

0.68

Loss of sheet (P = 0.0315);.;

MVP

0.87

MPC

0.26

ClinPred

0.45

GERP RS

4.1

Varity_R

0.22

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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