NM_001368882.1:c.1485+393G>A

Variant names:

• chr10-69929392-G-A
• rs2637229
• NM_001368882.1:c.1485+393G>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.1485+393G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 151,530 control chromosomes in the GnomAD database, including 26,072 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 0.59 (26072 hom., cov: 29)
• Consequence: COL13A1 NM_001368882.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL13A1	NM_001368882.1	c.1485+393G>A		intron_variant	Intron 28 of 40	ENST00000645393.2	NP_001355811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL13A1	ENST00000645393.2	c.1485+393G>A		intron_variant	Intron 28 of 40		NM_001368882.1	ENSP00000496051.1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88786 AN: 151412 Hom.: 26052 Cov.: 29

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.586 AC: 88832 AN: 151530 Hom.: 26072 Cov.: 29 AF XY: 0.587 AC XY: 43423 AN XY: 73996

African (AFR) AF: 0.613 AC: 25305 AN: 41264

American (AMR) AF: 0.594 AC: 9061 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2130 AN: 3470

East Asian (EAS) AF: 0.525 AC: 2700 AN: 5144

South Asian (SAS) AF: 0.480 AC: 2299 AN: 4786

European-Finnish (FIN) AF: 0.659 AC: 6869 AN: 10430

Middle Eastern (MID) AF: 0.552 AC: 160 AN: 290

European-Non Finnish (NFE) AF: 0.568 AC: 38529 AN: 67880

Other (OTH) AF: 0.590 AC: 1244 AN: 2108

Alfa AF: 0.568 Hom.: 79121

Bravo AF: 0.582

Asia WGS AF: 0.518 AC: 1805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.65
PhyloP100		0.28
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: rs2637229; hg19: chr10-71689148;