Variant 10-69802448-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001368882.1(COL13A1):c.25G>A(p.Ala9Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000333 in 1,503,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

COL13A1
NM_001368882.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36029518).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL13A1	NM_001368882.1 linkuse as main transcript	c.25G>A	p.Ala9Thr	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.25G>A	p.Ala9Thr	missense_variant	1/41		NM_001368882.1	ENSP00000496051	P1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.00000148

AC:

AN:

1351466

Hom.:

Cov.:

AF XY:

0.00000300

AC XY:

AN XY:

666446

show subpopulations

Gnomad4 AFR exome

AF:

0.0000756

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

The c.25G>A (p.A9T) alteration is located in exon 1 (coding exon 1) of the COL13A1 gene. This alteration results from a G to A substitution at nucleotide position 25, causing the alanine (A) at amino acid position 9 to be replaced by a threonine (T). 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

0.092

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.066

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

Eigen

Benign

0.12

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.88

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

M_CAP

Pathogenic

0.54

MetaRNN

Benign

0.36

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

MetaSVM

Uncertain

0.31

MutationAssessor

Benign

0.0

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

MutationTaster

Benign

0.97

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

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.23

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

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

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

Sift4G

Benign

0.085

.;T;D;D;T;T;T;T;T

Polyphen

0.99, 0.88

.;D;P;P;.;.;P;P;.

Vest4

0.29, 0.28, 0.27, 0.37, 0.39, 0.38, 0.37, 0.34

MutPred

0.17

Gain of glycosylation at A9 (P = 0.0504);Gain of glycosylation at A9 (P = 0.0504);Gain of glycosylation at A9 (P = 0.0504);Gain of glycosylation at A9 (P = 0.0504);Gain of glycosylation at A9 (P = 0.0504);Gain of glycosylation at A9 (P = 0.0504);Gain of glycosylation at A9 (P = 0.0504);Gain of glycosylation at A9 (P = 0.0504);Gain of glycosylation at A9 (P = 0.0504);

MVP

0.83

MPC

2.4

ClinPred

0.78

GERP RS

4.0

Varity_R

0.20

gMVP

0.40

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

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