10-69823442-C-T

Variant names:

• chr10-69823442-C-T
• rs7077164
• NM_001368882.1:c.364+1004C>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.364+1004C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,970 control chromosomes in the GnomAD database, including 10,393 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 0.36 (10393 hom., cov: 32)
• Consequence: COL13A1 NM_001368882.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL13A1	NM_001368882.1	c.364+1004C>T		intron_variant	Intron 2 of 40	ENST00000645393.2	NP_001355811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL13A1	ENST00000645393.2	c.364+1004C>T		intron_variant	Intron 2 of 40		NM_001368882.1	ENSP00000496051.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54929 AN: 151854 Hom.: 10359 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.362 AC: 55013 AN: 151970 Hom.: 10393 Cov.: 32 AF XY: 0.361 AC XY: 26781 AN XY: 74254

African (AFR) AF: 0.464 AC: 19217 AN: 41426

American (AMR) AF: 0.422 AC: 6444 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 852 AN: 3466

East Asian (EAS) AF: 0.410 AC: 2113 AN: 5152

South Asian (SAS) AF: 0.251 AC: 1206 AN: 4812

European-Finnish (FIN) AF: 0.251 AC: 2650 AN: 10550

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21436 AN: 67974

Other (OTH) AF: 0.374 AC: 790 AN: 2114

Alfa AF: 0.334 Hom.: 37505

Bravo AF: 0.379

Asia WGS AF: 0.333 AC: 1162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.50
PhyloP100		-0.31
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: rs7077164; hg19: chr10-71583198;