chr20-63307997-C-T

Variant names:

• chr20-63307997-C-T
• rs1017703401
• NM_020882.4:c.682C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020882.4(COL20A1):​c.682C>T​(p.Gln228*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: COL20A1 NM_020882.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hereditary palmoplantar keratoderma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020882.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL20A1	NM_020882.4	MANE Select	c.682C>T	p.Gln228*	stop_gained	Exon 7 of 36	NP_065933.2	Q9P218-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL20A1	ENST00000358894.11	TSL:1 MANE Select	c.682C>T	p.Gln228*	stop_gained	Exon 7 of 36	ENSP00000351767.6	Q9P218-1
	COL20A1	ENST00000479501.5	TSL:1	n.744C>T		non_coding_transcript_exon	Exon 7 of 36
	COL20A1	ENST00000894509.1		c.682C>T	p.Gln228*	stop_gained	Exon 7 of 37	ENSP00000564568.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.51
CADD	Pathogenic	35
DANN	Uncertain	1.0
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.012
FATHMM_MKL	Benign	0.31	N
PhyloP100		0.23
Vest4		0.17
GERP RS		3.1
Mutation Taster		=50/150	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1017703401; hg19: chr20-61939349;