rs17497526

Variant names:

• chr10-69820364-T-C
• rs17497526
• NM_001368882.1:c.295-2005T>C

Variant summary

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

The NM_001368882.1(COL13A1):​c.295-2005T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 152,286 control chromosomes in the GnomAD database, including 387 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 0.061 (387 hom., cov: 33)
• Consequence: COL13A1 NM_001368882.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333
• Publications: 11 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

ENSG00000289193 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL13A1	NM_001368882.1	c.295-2005T>C		intron_variant	Intron 1 of 40	ENST00000645393.2	NP_001355811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL13A1	ENST00000645393.2	c.295-2005T>C		intron_variant	Intron 1 of 40		NM_001368882.1	ENSP00000496051.1

Frequencies

GnomAD3 genomes AF: 0.0610 AC: 9286 AN: 152168 Hom.: 388 Cov.: 33

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.0676

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.0965

Gnomad SAS AF: 0.0387

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.0678

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

GnomAD4 genome AF: 0.0610 AC: 9287 AN: 152286 Hom.: 387 Cov.: 33 AF XY: 0.0620 AC XY: 4618 AN XY: 74454

African (AFR) AF: 0.0143 AC: 594 AN: 41568

American (AMR) AF: 0.0675 AC: 1034 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 137 AN: 3468

East Asian (EAS) AF: 0.0969 AC: 501 AN: 5172

South Asian (SAS) AF: 0.0390 AC: 188 AN: 4824

European-Finnish (FIN) AF: 0.104 AC: 1099 AN: 10602

Middle Eastern (MID) AF: 0.0582 AC: 17 AN: 292

European-Non Finnish (NFE) AF: 0.0811 AC: 5517 AN: 68026

Other (OTH) AF: 0.0666 AC: 141 AN: 2116

Alfa AF: 0.0741 Hom.: 746

Bravo AF: 0.0571

Asia WGS AF: 0.0640 AC: 224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.9
DANN	Benign	0.82
PhyloP100		-0.33
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: rs17497526; hg19: chr10-71580120;