20-63305938-G-A

Variant names:

• chr20-63305938-G-A
• NM_020882.4:c.395G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020882.4(COL20A1):​c.395G>A​(p.Gly132Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: COL20A1 NM_020882.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.220

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]

ACMG classification

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=0.09862101).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL20A1	NM_020882.4	c.395G>A	p.Gly132Glu	missense_variant	Exon 5 of 36	ENST00000358894.11	NP_065933.2
COL20A1	XM_011528937.2	c.395G>A	p.Gly132Glu	missense_variant	Exon 5 of 36		XP_011527239.1
COL20A1	XM_011528938.2	c.395G>A	p.Gly132Glu	missense_variant	Exon 5 of 36		XP_011527240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL20A1	ENST00000358894.11	c.395G>A	p.Gly132Glu	missense_variant	Exon 5 of 36	1	NM_020882.4	ENSP00000351767.6
COL20A1	ENST00000479501.5	n.457G>A		non_coding_transcript_exon_variant	Exon 5 of 36	1
COL20A1	ENST00000422202.5	c.395G>A	p.Gly132Glu	missense_variant	Exon 4 of 35	5		ENSP00000414753.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.395G>A (p.G132E) alteration is located in exon 5 (coding exon 4) of the COL20A1 gene. This alteration results from a G to A substitution at nucleotide position 395, causing the glycine (G) at amino acid position 132 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	0.066
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	2.5
DANN	Benign	0.64
DEOGEN2	Benign	0.0067	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.34	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.099	T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.55	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.11	N;N
REVEL	Benign	0.11
Sift	Benign	0.20	T;T
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.26	B;.
Vest4		0.098
MutPred		0.24		Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);
MVP		0.60
MPC		0.056
ClinPred		0.14	T
GERP RS		0.096
Varity_R		0.037
gMVP		0.035

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-61937290;