Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001368882.1(COL13A1):c.525A>C(p.Gly175Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,611,854 control chromosomes in the GnomAD database, including 9,499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 895 hom., cov: 31)

Exomes 𝑓: 0.11 ( 8604 hom. )

Consequence

COL13A1
NM_001368882.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.294

Publications

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

COL13A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 10-69887467-A-C is Benign according to our data. Variant chr10-69887467-A-C is described in ClinVar as Benign. ClinVar VariationId is 1217334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.294 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

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
COL13A1	NM_001368882.1	MANE Select	c.525A>C	p.Gly175Gly	synonymous	Exon 8 of 41	NP_001355811.1
COL13A1	NM_001130103.2		c.498A>C	p.Gly166Gly	synonymous	Exon 7 of 40	NP_001123575.1
COL13A1	NM_080801.4		c.498A>C	p.Gly166Gly	synonymous	Exon 7 of 39	NP_542991.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
COL13A1	ENST00000645393.2	MANE Select	c.525A>C	p.Gly175Gly	synonymous	Exon 8 of 41	ENSP00000496051.1
COL13A1	ENST00000398978.8	TSL:5	c.498A>C	p.Gly166Gly	synonymous	Exon 7 of 40	ENSP00000381949.3
COL13A1	ENST00000354547.7	TSL:5	c.498A>C	p.Gly166Gly	synonymous	Exon 7 of 39	ENSP00000346553.3

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16067

AN:

151202

Hom.:

896

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0995

Gnomad AMI

AF:

0.157

Gnomad AMR

AF:

0.0897

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.0766

Gnomad SAS

AF:

0.0789

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.113

Gnomad OTH

AF:

0.128

GnomAD2 exomes

AF:

0.100

AC:

24846

AN:

248540

AF XY:

0.101

show subpopulations

Gnomad AFR exome

AF:

0.0944

Gnomad AMR exome

AF:

0.0548

Gnomad ASJ exome

AF:

0.197

Gnomad EAS exome

AF:

0.0894

Gnomad FIN exome

AF:

0.107

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.106

AC:

154669

AN:

1460536

Hom.:

8604

Cov.:

AF XY:

0.106

AC XY:

76730

AN XY:

726584

show subpopulations

African (AFR)

AF:

0.101

AC:

3370

AN:

33462

American (AMR)

AF:

0.0576

AC:

2573

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

5208

AN:

26114

East Asian (EAS)

AF:

0.0651

AC:

2582

AN:

39692

South Asian (SAS)

AF:

0.0750

AC:

6463

AN:

86176

European-Finnish (FIN)

AF:

0.106

AC:

5647

AN:

53312

Middle Eastern (MID)

AF:

0.194

AC:

1115

AN:

5756

European-Non Finnish (NFE)

AF:

0.109

AC:

120931

AN:

1110978

Other (OTH)

AF:

0.112

AC:

6780

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

7122

14244

21367

28489

35611

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4342

8684

13026

17368

21710

<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

AF:

0.106

AC:

16068

AN:

151318

Hom.:

895

Cov.:

AF XY:

0.106

AC XY:

7791

AN XY:

73838

show subpopulations

African (AFR)

AF:

0.0994

AC:

4100

AN:

41232

American (AMR)

AF:

0.0896

AC:

1364

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.192

AC:

665

AN:

3464

East Asian (EAS)

AF:

0.0764

AC:

392

AN:

5130

South Asian (SAS)

AF:

0.0785

AC:

374

AN:

4764

European-Finnish (FIN)

AF:

0.101

AC:

1050

AN:

10392

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.113

AC:

7638

AN:

67808

Other (OTH)

AF:

0.128

AC:

268

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

720

1441

2161

2882

3602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

186

372

558

744

930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.112

Hom.:

785

Bravo

AF:

0.104

Asia WGS

AF:

0.0770

AC:

267

AN:

3478

EpiCase

AF:

0.115

EpiControl

AF:

0.113

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Congenital myasthenic syndrome 19 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

0.29

Mutation Taster

=99/1

polymorphism (auto)

(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

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over