Genetic Variant NM_020882.4:c.413C>T (chr20-63305956-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2

The NM_020882.4(COL20A1):c.413C>T(p.Pro138Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P138R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

COL20A1
NM_020882.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0420

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

hereditary palmoplantar keratoderma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

COL20A1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.102336586).

BS2

High AC in GnomAdExome4 at 5 AD gene.

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.413C>T	p.Pro138Leu	missense	Exon 5 of 36	NP_065933.2	Q9P218-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COL20A1	ENST00000358894.11	TSL:1 MANE Select	c.413C>T	p.Pro138Leu	missense	Exon 5 of 36	ENSP00000351767.6	Q9P218-1
COL20A1	ENST00000479501.5	TSL:1	n.475C>T		non_coding_transcript_exon	Exon 5 of 36
COL20A1	ENST00000894509.1		c.413C>T	p.Pro138Leu	missense	Exon 5 of 37	ENSP00000564568.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460388

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726482

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111714

Other (OTH)

AF:

0.00

AC:

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000274

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.0063

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.60

M_CAP

Benign

0.073

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.90

PhyloP100

0.042

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.4

REVEL

Benign

0.059

Sift

Benign

0.14

Sift4G

Benign

0.13

Polyphen

0.0010

Vest4

0.12

MutPred

0.22

Gain of sheet (P = 0.0221)

MVP

0.77

MPC

0.035

ClinPred

0.065

GERP RS

1.6

Varity_R

0.050

gMVP

0.055

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over