chr10-69802436-C-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001368882.1(COL13A1):c.13C>A(p.Arg5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000002 in 1,500,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R5C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

COL13A1
NM_001368882.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.13

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

congenital myasthenic syndrome 19
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
presynaptic congenital myasthenic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
postsynaptic congenital myasthenic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

COL13A1 links:

ENSG00000289193 (HGNC:):

ENSG00000289193 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1630364).

BP6

Variant 10-69802436-C-A is Benign according to our data. Variant chr10-69802436-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3834962.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001368882.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COL13A1	NM_001368882.1	MANE Select	c.13C>A	p.Arg5Ser	missense	Exon 1 of 41	NP_001355811.1	A0A2R8YGI3
COL13A1	NM_001130103.2		c.13C>A	p.Arg5Ser	missense	Exon 1 of 40	NP_001123575.1	Q5TAT6-1
COL13A1	NM_080801.4		c.13C>A	p.Arg5Ser	missense	Exon 1 of 39	NP_542991.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COL13A1	ENST00000645393.2	MANE Select	c.13C>A	p.Arg5Ser	missense	Exon 1 of 41	ENSP00000496051.1	A0A2R8YGI3
COL13A1	ENST00000398978.8	TSL:5	c.13C>A	p.Arg5Ser	missense	Exon 1 of 40	ENSP00000381949.3	Q5TAT6-1
COL13A1	ENST00000354547.7	TSL:5	c.13C>A	p.Arg5Ser	missense	Exon 1 of 39	ENSP00000346553.3	Q5TAT6-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

1347936

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

664596

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26316

American (AMR)

AF:

0.0000409

AC:

AN:

24472

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23006

East Asian (EAS)

AF:

0.00

AC:

AN:

31764

South Asian (SAS)

AF:

0.00

AC:

AN:

72560

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5270

European-Non Finnish (NFE)

AF:

9.41e-7

AC:

AN:

1062386

Other (OTH)

AF:

0.00

AC:

AN:

55534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41430

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.068

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.71

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.16

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

0.0

PhyloP100

1.1

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.73

REVEL

Benign

0.18

Sift

Benign

0.053

Sift4G

Uncertain

0.0090

Polyphen

0.057

Vest4

0.16

MutPred

0.43

Loss of MoRF binding (P = 0.0082)

MVP

0.62

MPC

1.4

ClinPred

0.081

GERP RS

-1.2

PromoterAI

0.011

Neutral

(source)

Varity_R

0.095

gMVP

0.32

Mutation Taster

=89/11

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over