10-69802338-C-T

Variant names:

• chr10-69802338-C-T
• rs56825061
• NM_001368882.1:c.-86C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001368882.1(COL13A1):​c.-86C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00954 in 1,338,856 control chromosomes in the GnomAD database, including 1,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (642 hom., cov: 34)
  • Exomes 𝑓: 0.0043 (403 hom.)
• Consequence: COL13A1 NM_001368882.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.469
• 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

ENSG00000289193 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 10-69802338-C-T is Benign according to our data. Variant chr10-69802338-C-T is described in ClinVar as Benign. ClinVar VariationId is 1237469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 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.-86C>T		5_prime_UTR	Exon 1 of 41	NP_001355811.1	A0A2R8YGI3
	COL13A1	NM_001130103.2		c.-86C>T		5_prime_UTR	Exon 1 of 40	NP_001123575.1	Q5TAT6-1
	COL13A1	NM_080801.4		c.-86C>T		5_prime_UTR	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.-86C>T		5_prime_UTR	Exon 1 of 41	ENSP00000496051.1	A0A2R8YGI3
	COL13A1	ENST00000398978.8	TSL:5	c.-86C>T		5_prime_UTR	Exon 1 of 40	ENSP00000381949.3	Q5TAT6-1
	COL13A1	ENST00000354547.7	TSL:5	c.-86C>T		5_prime_UTR	Exon 1 of 39	ENSP00000346553.3	Q5TAT6-2

Frequencies

GnomAD3 genomes AF: 0.0502 AC: 7637 AN: 152190 Hom.: 638 Cov.: 34

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0169

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0387

GnomAD4 exome AF: 0.00429 AC: 5096 AN: 1186548 Hom.: 403 Cov.: 20 AF XY: 0.00383 AC XY: 2204 AN XY: 575334

African (AFR) AF: 0.180 AC: 4107 AN: 22792

American (AMR) AF: 0.0131 AC: 146 AN: 11126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16720

East Asian (EAS) AF: 0.00 AC: 0 AN: 27936

South Asian (SAS) AF: 0.000440 AC: 23 AN: 52230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32792

Middle Eastern (MID) AF: 0.00845 AC: 29 AN: 3430

European-Non Finnish (NFE) AF: 0.000221 AC: 214 AN: 970426

Other (OTH) AF: 0.0118 AC: 577 AN: 49096

GnomAD4 genome AF: 0.0504 AC: 7673 AN: 152308 Hom.: 642 Cov.: 34 AF XY: 0.0485 AC XY: 3609 AN XY: 74488

African (AFR) AF: 0.176 AC: 7294 AN: 41536

American (AMR) AF: 0.0169 AC: 259 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68032

Other (OTH) AF: 0.0383 AC: 81 AN: 2116

Alfa AF: 0.0331 Hom.: 104

Bravo AF: 0.0572

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	14
DANN	Benign	0.85
PhyloP100		0.47
PromoterAI		0.043	Neutral
Mutation Taster		=300/0	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: rs56825061; hg19: chr10-71562094;