10-69802452-C-T

Position:

chr10-69802452-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001368882.1(COL13A1):c.29C>T(p.Ala10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000931 in 1,503,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

COL13A1
NM_001368882.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.164

Variant links:

Genes affected

COL13A1 (HGNC:2190): (collagen type XIII alpha 1 chain) This gene encodes the alpha chain of one of the nonfibrillar collagens. The function of this gene product is not known, however, it has been detected at low levels in all connective tissue-producing cells so it may serve a general function in connective tissues. Unlike most of the collagens, which are secreted into the extracellular matrix, collagen XIII contains a transmembrane domain and the protein has been localized to the plasma membrane. The transcripts for this gene undergo complex and extensive splicing involving at least eight exons. Like other collagens, collagen XIII is a trimer; it is not known whether this trimer is composed of one or more than one alpha chain isomer. A number of alternatively spliced transcript variants have been described, but the full length nature of some of them has not been determined. [provided by RefSeq, Jul 2008]

COL13A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.08427474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL13A1	NM_001368882.1 linkuse as main transcript	c.29C>T	p.Ala10Val	missense_variant	1/41	ENST00000645393.2	NP_001355811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL13A1	ENST00000645393.2 linkuse as main transcript	c.29C>T	p.Ala10Val	missense_variant	1/41		NM_001368882.1	ENSP00000496051	P1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000888

AC:

AN:

1351604

Hom.:

Cov.:

AF XY:

0.00000600

AC XY:

AN XY:

666512

show subpopulations

Gnomad4 AFR exome

AF:

0.000113

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000410

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000108

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000378

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.000173

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 23, 2021

This sequence change replaces alanine with valine at codon 10 of the COL13A1 protein (p.Ala10Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with COL13A1-related conditions. While this variant is present in population databases (rs376791843), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.11

.;T;.;.;.;T;.;.;.

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.043

LIST_S2

Uncertain

0.87

D;D;D;D;D;D;D;D;D

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.084

T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.24

MutationAssessor

Benign

0.0

.;N;N;N;N;.;N;N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.92

.;N;N;N;N;N;N;N;N

REVEL

Benign

0.087

Sift

Uncertain

0.0070

.;D;D;D;D;D;D;D;D

Sift4G

Benign

0.24

.;T;T;T;T;T;T;T;T

Polyphen

0.018, 0.0020

.;B;B;B;.;.;B;B;.

Vest4

0.15, 0.16, 0.16, 0.23, 0.24, 0.19, 0.24, 0.24

MutPred

0.22

Loss of ubiquitination at K8 (P = 0.0345);Loss of ubiquitination at K8 (P = 0.0345);Loss of ubiquitination at K8 (P = 0.0345);Loss of ubiquitination at K8 (P = 0.0345);Loss of ubiquitination at K8 (P = 0.0345);Loss of ubiquitination at K8 (P = 0.0345);Loss of ubiquitination at K8 (P = 0.0345);Loss of ubiquitination at K8 (P = 0.0345);Loss of ubiquitination at K8 (P = 0.0345);

MVP

0.62

MPC

1.3

ClinPred

0.058

GERP RS

2.5

Varity_R

0.058

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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