chr10-69880499-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001368882.1(COL13A1):c.463-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,603,484 control chromosomes in the GnomAD database, including 27,850 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3307 hom., cov: 32)

Exomes 𝑓: 0.16 ( 24543 hom. )

Consequence

COL13A1
NM_001368882.1 splice_region, intron

Scores

Splicing: ADA: 0.00003695

Clinical Significance

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

Conservation

PhyloP100: 0.704

Publications

10 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 10-69880499-G-A is Benign according to our data. Variant chr10-69880499-G-A is described in ClinVar as Benign. ClinVar VariationId is 1217332.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.44 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	Effect	Exon Rank	Protein
COL13A1	NM_001368882.1	MANE Select	c.463-4G>A	splice_region intron	N/A	NP_001355811.1
COL13A1	NM_001368886.1		c.-142G>A	5_prime_UTR	Exon 6 of 37	NP_001355815.1
COL13A1	NM_001130103.2		c.436-4G>A	splice_region intron	N/A	NP_001123575.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
COL13A1	ENST00000645393.2	MANE Select	c.463-4G>A	splice_region intron	N/A	ENSP00000496051.1
COL13A1	ENST00000398978.8	TSL:5	c.436-4G>A	splice_region intron	N/A	ENSP00000381949.3
COL13A1	ENST00000354547.7	TSL:5	c.436-4G>A	splice_region intron	N/A	ENSP00000346553.3

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

29624

AN:

151806

Hom.:

3291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.234

Gnomad AMI

AF:

0.0989

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.143

Gnomad EAS

AF:

0.455

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.202

Gnomad MID

AF:

0.128

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.167

GnomAD2 exomes

AF:

0.219

AC:

53842

AN:

245334

AF XY:

0.217

show subpopulations

Gnomad AFR exome

AF:

0.240

Gnomad AMR exome

AF:

0.310

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.448

Gnomad FIN exome

AF:

0.212

Gnomad NFE exome

AF:

0.136

Gnomad OTH exome

AF:

0.188

GnomAD4 exome

AF:

0.165

AC:

239223

AN:

1451562

Hom.:

24543

Cov.:

AF XY:

0.168

AC XY:

121714

AN XY:

722590

show subpopulations

African (AFR)

AF:

0.232

AC:

7728

AN:

33278

American (AMR)

AF:

0.299

AC:

13308

AN:

44504

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

3559

AN:

26020

East Asian (EAS)

AF:

0.476

AC:

18830

AN:

39566

South Asian (SAS)

AF:

0.308

AC:

26478

AN:

85930

European-Finnish (FIN)

AF:

0.208

AC:

11103

AN:

53292

Middle Eastern (MID)

AF:

0.146

AC:

839

AN:

5728

European-Non Finnish (NFE)

AF:

0.133

AC:

146550

AN:

1103272

Other (OTH)

AF:

0.181

AC:

10828

AN:

59972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

8924

17848

26773

35697

44621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5622

11244

16866

22488

28110

<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:

0.195

AC:

29661

AN:

151922

Hom.:

3307

Cov.:

AF XY:

0.201

AC XY:

14933

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.234

AC:

9699

AN:

41368

American (AMR)

AF:

0.233

AC:

3567

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

496

AN:

3472

East Asian (EAS)

AF:

0.455

AC:

2332

AN:

5124

South Asian (SAS)

AF:

0.315

AC:

1514

AN:

4812

European-Finnish (FIN)

AF:

0.202

AC:

2136

AN:

10566

Middle Eastern (MID)

AF:

0.128

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.139

AC:

9432

AN:

67992

Other (OTH)

AF:

0.170

AC:

358

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1177

2353

3530

4706

5883

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

334

668

1002

1336

1670

<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:

0.144

Hom.:

1325

Bravo

AF:

0.199

Asia WGS

AF:

0.380

AC:

1319

AN:

3478

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

-0.76

CADD

Benign

5.5

(source)

DANN

Benign

0.59

PhyloP100

0.70

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000037

dbscSNV1_RF

Benign

0.0040

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over