chr10-69828748-G-A

Variant names:

• chr10-69828748-G-A
• rs1227756
• NM_001368882.1:c.364+6310G>A

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+6310G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,016 control chromosomes in the GnomAD database, including 17,141 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 0.47 (17141 hom., cov: 33)
• Consequence: COL13A1 NM_001368882.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289
• Publications: 32 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.54 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+6310G>A		intron	N/A	NP_001355811.1
	COL13A1	NM_001130103.2		c.364+6310G>A		intron	N/A	NP_001123575.1
	COL13A1	NM_080801.4		c.364+6310G>A		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+6310G>A		intron	N/A	ENSP00000496051.1
	COL13A1	ENST00000398978.8	TSL:5	c.364+6310G>A		intron	N/A	ENSP00000381949.3
	COL13A1	ENST00000354547.7	TSL:5	c.364+6310G>A		intron	N/A	ENSP00000346553.3

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70968 AN: 151898 Hom.: 17134 Cov.: 33

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.467 AC: 70980 AN: 152016 Hom.: 17141 Cov.: 33 AF XY: 0.460 AC XY: 34163 AN XY: 74298

African (AFR) AF: 0.368 AC: 15260 AN: 41432

American (AMR) AF: 0.404 AC: 6180 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2188 AN: 3470

East Asian (EAS) AF: 0.277 AC: 1427 AN: 5158

South Asian (SAS) AF: 0.465 AC: 2242 AN: 4820

European-Finnish (FIN) AF: 0.476 AC: 5027 AN: 10564

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37018 AN: 67970

Other (OTH) AF: 0.455 AC: 963 AN: 2116

Alfa AF: 0.513 Hom.: 73720

Bravo AF: 0.456

Asia WGS AF: 0.348 AC: 1211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.2
DANN	Benign	0.84
PhyloP100		0.29
Mutation Taster		=99/1	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: rs1227756; hg19: chr10-71588504;