20-63307573-C-T

Variant names:

• chr20-63307573-C-T
• NM_020882.4:c.580C>T

Variant summary

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

The NM_020882.4(COL20A1):​c.580C>T​(p.His194Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,368 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: COL20A1 NM_020882.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.14

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL20A1	NM_020882.4	c.580C>T	p.His194Tyr	missense_variant	Exon 6 of 36	ENST00000358894.11	NP_065933.2
COL20A1	XM_011528937.2	c.580C>T	p.His194Tyr	missense_variant	Exon 6 of 36		XP_011527239.1
COL20A1	XM_011528938.2	c.580C>T	p.His194Tyr	missense_variant	Exon 6 of 36		XP_011527240.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL20A1	ENST00000358894.11	c.580C>T	p.His194Tyr	missense_variant	Exon 6 of 36	1	NM_020882.4	ENSP00000351767.6
COL20A1	ENST00000479501.5	n.642C>T		non_coding_transcript_exon_variant	Exon 6 of 36	1
COL20A1	ENST00000422202.5	c.601C>T	p.His201Tyr	missense_variant	Exon 5 of 35	5		ENSP00000414753.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460368 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726468

Gnomad4 AFR exome AF: 0.00

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.580C>T (p.H194Y) alteration is located in exon 6 (coding exon 5) of the COL20A1 gene. This alteration results from a C to T substitution at nucleotide position 580, causing the histidine (H) at amino acid position 194 to be replaced by a tyrosine (Y). 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	0.17
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T;.
Eigen	Benign	-0.057
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.75	T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0020	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.93	P;P
Vest4		0.37
MutPred		0.65		Loss of disorder (P = 0.1248);.;
MVP		0.85
MPC		0.24
ClinPred		0.94	D
GERP RS		1.7
Varity_R		0.47
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr20-61938925;