10-69802452-C-G

Variant names:

• chr10-69802452-C-G
• rs376791843
• NM_001368882.1:c.29C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001368882.1(COL13A1):​c.29C>G​(p.Ala10Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000222 in 1,351,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A10V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: COL13A1 NM_001368882.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09906742).

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.29C>G	p.Ala10Gly	missense	Exon 1 of 41	NP_001355811.1	A0A2R8YGI3
	COL13A1	NM_001130103.2		c.29C>G	p.Ala10Gly	missense	Exon 1 of 40	NP_001123575.1	Q5TAT6-1
	COL13A1	NM_080801.4		c.29C>G	p.Ala10Gly	missense	Exon 1 of 39	NP_542991.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL13A1	ENST00000645393.2	MANE Select	c.29C>G	p.Ala10Gly	missense	Exon 1 of 41	ENSP00000496051.1	A0A2R8YGI3
	COL13A1	ENST00000398978.8	TSL:5	c.29C>G	p.Ala10Gly	missense	Exon 1 of 40	ENSP00000381949.3	Q5TAT6-1
	COL13A1	ENST00000354547.7	TSL:5	c.29C>G	p.Ala10Gly	missense	Exon 1 of 39	ENSP00000346553.3	Q5TAT6-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000222 AC: 3 AN: 1351604 Hom.: 0 Cov.: 30 AF XY: 0.00000300 AC XY: 2 AN XY: 666512

African (AFR) AF: 0.00 AC: 0 AN: 26480

American (AMR) AF: 0.00 AC: 0 AN: 25114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23204

East Asian (EAS) AF: 0.00 AC: 0 AN: 31950

South Asian (SAS) AF: 0.00 AC: 0 AN: 73162

European-Finnish (FIN) AF: 0.0000427 AC: 2 AN: 46818

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5328

European-Non Finnish (NFE) AF: 9.40e-7 AC: 1 AN: 1063838

Other (OTH) AF: 0.00 AC: 0 AN: 55710

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.046	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.65	T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.099	T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.16
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	1.3	N
REVEL	Benign	0.097
Sift	Benign	0.050	D
Sift4G	Benign	0.51	T
Polyphen		0.034	B
Vest4		0.18
MutPred		0.18		Loss of stability (P = 0.0441)
MVP		0.63
MPC		1.4
ClinPred		0.069	T
GERP RS		2.5
PromoterAI		-0.017	Neutral
Varity_R		0.048
gMVP		0.22
Mutation Taster		=74/26	polymorphism

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: rs376791843; hg19: chr10-71562208;