rs57703465

Variant names:

• chr10-69881312-G-A
• rs57703465
• NM_001368882.1:c.513+759G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-69881312-G-A
• chr10-69881312-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.513+759G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 151,858 control chromosomes in the GnomAD database, including 1,305 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 0.12 (1305 hom., cov: 32)
• Consequence: COL13A1 NM_001368882.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• 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: 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL13A1	NM_001368882.1	c.513+759G>A		intron_variant	Intron 7 of 40	ENST00000645393.2	NP_001355811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL13A1	ENST00000645393.2	c.513+759G>A		intron_variant	Intron 7 of 40		NM_001368882.1	ENSP00000496051.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17981 AN: 151738 Hom.: 1300 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0845

Gnomad OTH AF: 0.0879

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

GnomAD4 genome AF: 0.119 AC: 18001 AN: 151858 Hom.: 1305 Cov.: 32 AF XY: 0.123 AC XY: 9154 AN XY: 74208

African (AFR) AF: 0.141 AC: 5837 AN: 41386

American (AMR) AF: 0.110 AC: 1680 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 228 AN: 3468

East Asian (EAS) AF: 0.356 AC: 1829 AN: 5132

South Asian (SAS) AF: 0.186 AC: 891 AN: 4796

European-Finnish (FIN) AF: 0.148 AC: 1562 AN: 10564

Middle Eastern (MID) AF: 0.0240 AC: 7 AN: 292

European-Non Finnish (NFE) AF: 0.0845 AC: 5739 AN: 67920

Other (OTH) AF: 0.0913 AC: 192 AN: 2104

Alfa AF: 0.0594 Hom.: 94

Bravo AF: 0.116

Asia WGS AF: 0.269 AC: 937 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.041
DANN	Benign	0.61
PhyloP100		-1.3
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: rs57703465; hg19: chr10-71641068;