10-69889553-A-G

Variant names:

• chr10-69889553-A-G
• rs2683572
• NM_001368882.1:c.603+113A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001368882.1(COL13A1):​c.603+113A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 1,375,432 control chromosomes in the GnomAD database, including 456,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (48399 hom., cov: 33)
  • Exomes 𝑓: 0.81 (408040 hom.)
• Consequence: COL13A1 NM_001368882.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.28
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 10-69889553-A-G is Benign according to our data. Variant chr10-69889553-A-G is described in ClinVar as Benign. ClinVar VariationId is 1274483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.83 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL13A1	NM_001368882.1	MANE Select	c.603+113A>G		intron	N/A	NP_001355811.1
	COL13A1	NM_001130103.2		c.576+113A>G		intron	N/A	NP_001123575.1
	COL13A1	NM_080801.4		c.576+113A>G		intron	N/A	NP_542991.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL13A1	ENST00000645393.2	MANE Select	c.603+113A>G		intron	N/A	ENSP00000496051.1
	COL13A1	ENST00000398978.8	TSL:5	c.576+113A>G		intron	N/A	ENSP00000381949.3
	COL13A1	ENST00000354547.7	TSL:5	c.576+113A>G		intron	N/A	ENSP00000346553.3

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120877 AN: 152086 Hom.: 48372 Cov.: 33

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.851

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.826

GnomAD4 exome AF: 0.814 AC: 995191 AN: 1223228 Hom.: 408040 AF XY: 0.812 AC XY: 496531 AN XY: 611724

African (AFR) AF: 0.773 AC: 21625 AN: 27974

American (AMR) AF: 0.642 AC: 22934 AN: 35740

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 20256 AN: 23802

East Asian (EAS) AF: 0.543 AC: 19023 AN: 35006

South Asian (SAS) AF: 0.715 AC: 53835 AN: 75330

European-Finnish (FIN) AF: 0.845 AC: 41063 AN: 48604

Middle Eastern (MID) AF: 0.867 AC: 4614 AN: 5324

European-Non Finnish (NFE) AF: 0.837 AC: 769800 AN: 919258

Other (OTH) AF: 0.806 AC: 42041 AN: 52190

GnomAD4 genome AF: 0.795 AC: 120951 AN: 152204 Hom.: 48399 Cov.: 33 AF XY: 0.791 AC XY: 58869 AN XY: 74410

African (AFR) AF: 0.773 AC: 32111 AN: 41514

American (AMR) AF: 0.706 AC: 10803 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 2935 AN: 3466

East Asian (EAS) AF: 0.581 AC: 2998 AN: 5158

South Asian (SAS) AF: 0.694 AC: 3350 AN: 4828

European-Finnish (FIN) AF: 0.851 AC: 9028 AN: 10606

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.836 AC: 56846 AN: 68010

Other (OTH) AF: 0.822 AC: 1738 AN: 2114

Alfa AF: 0.803 Hom.: 31144

Bravo AF: 0.784

Asia WGS AF: 0.624 AC: 2171 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.75
PhyloP100		-4.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2683572; hg19: chr10-71649309; COSMIC: COSV62570801;