10-69844853-A-G

Variant names:

• chr10-69844853-A-G
• rs2704482
• NM_001368882.1:c.364+22415A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001368882.1(COL13A1):​c.364+22415A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,224 control chromosomes in the GnomAD database, including 50,018 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (50018 hom., cov: 34)
• Consequence: COL13A1 NM_001368882.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.913 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.364+22415A>G		intron	N/A	NP_001355811.1
	COL13A1	NM_001130103.2		c.364+22415A>G		intron	N/A	NP_001123575.1
	COL13A1	NM_080801.4		c.364+22415A>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.364+22415A>G		intron	N/A	ENSP00000496051.1
	COL13A1	ENST00000398978.8	TSL:5	c.364+22415A>G		intron	N/A	ENSP00000381949.3
	COL13A1	ENST00000354547.7	TSL:5	c.364+22415A>G		intron	N/A	ENSP00000346553.3

Frequencies

GnomAD3 genomes AF: 0.806 AC: 122591 AN: 152106 Hom.: 49988 Cov.: 34

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.825

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.935

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.822

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.809

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.806 AC: 122675 AN: 152224 Hom.: 50018 Cov.: 34 AF XY: 0.810 AC XY: 60285 AN XY: 74430

African (AFR) AF: 0.675 AC: 28049 AN: 41528

American (AMR) AF: 0.777 AC: 11897 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.825 AC: 2866 AN: 3472

East Asian (EAS) AF: 0.856 AC: 4421 AN: 5162

South Asian (SAS) AF: 0.936 AC: 4513 AN: 4824

European-Finnish (FIN) AF: 0.861 AC: 9128 AN: 10606

Middle Eastern (MID) AF: 0.822 AC: 240 AN: 292

European-Non Finnish (NFE) AF: 0.869 AC: 59115 AN: 68018

Other (OTH) AF: 0.812 AC: 1713 AN: 2110

Alfa AF: 0.775 Hom.: 17959

Bravo AF: 0.788

Asia WGS AF: 0.869 AC: 3022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.55
PhyloP100		-0.13
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: rs2704482; hg19: chr10-71604609;