rs10823435

Variant names:

• chr10-69819925-G-A
• rs10823435
• NM_001368882.1:c.295-2444G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-69819925-G-A
• chr10-69819925-G-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.295-2444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,144 control chromosomes in the GnomAD database, including 10,280 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 0.34 (10280 hom., cov: 32)
• Consequence: COL13A1 NM_001368882.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 2 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

ENSG00000289193 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.497 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.295-2444G>A		intron	N/A	NP_001355811.1	A0A2R8YGI3
	COL13A1	NM_001130103.2		c.295-2444G>A		intron	N/A	NP_001123575.1	Q5TAT6-1
	COL13A1	NM_080801.4		c.295-2444G>A		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.295-2444G>A		intron	N/A	ENSP00000496051.1	A0A2R8YGI3
	COL13A1	ENST00000398978.8	TSL:5	c.295-2444G>A		intron	N/A	ENSP00000381949.3	Q5TAT6-1
	COL13A1	ENST00000354547.7	TSL:5	c.295-2444G>A		intron	N/A	ENSP00000346553.3	Q5TAT6-2

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52362 AN: 152026 Hom.: 10281 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.344 AC: 52373 AN: 152144 Hom.: 10280 Cov.: 32 AF XY: 0.345 AC XY: 25647 AN XY: 74384

African (AFR) AF: 0.144 AC: 5979 AN: 41520

American (AMR) AF: 0.408 AC: 6244 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1669 AN: 3470

East Asian (EAS) AF: 0.396 AC: 2044 AN: 5158

South Asian (SAS) AF: 0.514 AC: 2478 AN: 4824

European-Finnish (FIN) AF: 0.383 AC: 4049 AN: 10580

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.418 AC: 28405 AN: 67988

Other (OTH) AF: 0.381 AC: 803 AN: 2108

Alfa AF: 0.374 Hom.: 1795

Bravo AF: 0.341

Asia WGS AF: 0.443 AC: 1538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.30
DANN	Benign	0.67
PhyloP100		-1.8
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: rs10823435; hg19: chr10-71579681;