10-69818146-C-T

Variant names:

• chr10-69818146-C-T
• rs1227771
• NM_001368882.1:c.295-4223C>T

Variant summary

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

The NM_001368882.1(COL13A1):​c.295-4223C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 152,040 control chromosomes in the GnomAD database, including 39,079 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 0.72 (39079 hom., cov: 31)
• Consequence: COL13A1 NM_001368882.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474
• 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

ENSG00000289193 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL13A1	NM_001368882.1	c.295-4223C>T		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.295-4223C>T		intron_variant	Intron 1 of 40		NM_001368882.1	ENSP00000496051.1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108807 AN: 151922 Hom.: 39057 Cov.: 31

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.649

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.701

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

GnomAD4 genome AF: 0.716 AC: 108880 AN: 152040 Hom.: 39079 Cov.: 31 AF XY: 0.713 AC XY: 53001 AN XY: 74302

African (AFR) AF: 0.646 AC: 26776 AN: 41430

American (AMR) AF: 0.649 AC: 9927 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.835 AC: 2900 AN: 3472

East Asian (EAS) AF: 0.757 AC: 3896 AN: 5148

South Asian (SAS) AF: 0.855 AC: 4124 AN: 4822

European-Finnish (FIN) AF: 0.709 AC: 7506 AN: 10580

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.755 AC: 51296 AN: 67980

Other (OTH) AF: 0.702 AC: 1479 AN: 2108

Alfa AF: 0.752 Hom.: 27253

Bravo AF: 0.709

Asia WGS AF: 0.798 AC: 2773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.7
DANN	Benign	0.38
PhyloP100		-0.47
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: rs1227771; hg19: chr10-71577902;