rs3858158

Variant names:

• chr10-69880294-T-C
• rs3858158
• NM_001368882.1:c.463-209T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001368882.1(COL13A1):​c.463-209T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 151,210 control chromosomes in the GnomAD database, including 3,109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (3109 hom., cov: 32)
• Consequence: COL13A1 NM_001368882.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.312
• Publications: 1 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-69880294-T-C is Benign according to our data. Variant chr10-69880294-T-C is described in ClinVar as Benign. ClinVar VariationId is 1278613.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL13A1	NM_001368882.1	MANE Select	c.463-209T>C		intron	N/A	NP_001355811.1	A0A2R8YGI3
	COL13A1	NM_001130103.2		c.436-209T>C		intron	N/A	NP_001123575.1	Q5TAT6-1
	COL13A1	NM_080801.4		c.436-209T>C		intron	N/A	NP_542991.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL13A1	ENST00000645393.2	MANE Select	c.463-209T>C		intron	N/A	ENSP00000496051.1	A0A2R8YGI3
	COL13A1	ENST00000398978.8	TSL:5	c.436-209T>C		intron	N/A	ENSP00000381949.3	Q5TAT6-1
	COL13A1	ENST00000354547.7	TSL:5	c.436-209T>C		intron	N/A	ENSP00000346553.3	Q5TAT6-2

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26508 AN: 151090 Hom.: 3092 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.0268

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.0765

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0997

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.176 AC: 26550 AN: 151210 Hom.: 3109 Cov.: 32 AF XY: 0.179 AC XY: 13201 AN XY: 73930

African (AFR) AF: 0.263 AC: 10870 AN: 41320

American (AMR) AF: 0.227 AC: 3447 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 409 AN: 3434

East Asian (EAS) AF: 0.471 AC: 2416 AN: 5128

South Asian (SAS) AF: 0.306 AC: 1453 AN: 4756

European-Finnish (FIN) AF: 0.0765 AC: 806 AN: 10538

Middle Eastern (MID) AF: 0.150 AC: 42 AN: 280

European-Non Finnish (NFE) AF: 0.0997 AC: 6735 AN: 67570

Other (OTH) AF: 0.167 AC: 348 AN: 2088

Alfa AF: 0.140 Hom.: 3150

Bravo AF: 0.189

Asia WGS AF: 0.390 AC: 1354 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.69
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: rs3858158; hg19: chr10-71640050;