10-69802014-G-A

Variant names:

• chr10-69802014-G-A
• rs2704505
• NM_001368882.1:c.-410G>A

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.-410G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.933 in 170,020 control chromosomes in the GnomAD database, including 74,402 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.93 (66122 hom., cov: 32)
  • Exomes 𝑓: 0.96 (8280 hom.)
• Consequence: COL13A1 NM_001368882.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0440
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-69802014-G-A is Benign according to our data. Variant chr10-69802014-G-A is described in ClinVar as Benign. ClinVar VariationId is 1269754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.978 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.-410G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 41	NP_001355811.1	A0A2R8YGI3
	COL13A1	NM_001368882.1	MANE Select	c.-410G>A		5_prime_UTR	Exon 1 of 41	NP_001355811.1	A0A2R8YGI3
	COL13A1	NM_001130103.2		c.-410G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 40	NP_001123575.1	Q5TAT6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL13A1	ENST00000645393.2	MANE Select	c.-410G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 41	ENSP00000496051.1	A0A2R8YGI3
	COL13A1	ENST00000645393.2	MANE Select	c.-410G>A		5_prime_UTR	Exon 1 of 41	ENSP00000496051.1	A0A2R8YGI3
	COL13A1	ENST00000398978.8	TSL:5	c.-410G>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 40	ENSP00000381949.3	Q5TAT6-1

Frequencies

GnomAD3 genomes AF: 0.930 AC: 141401 AN: 152100 Hom.: 66074 Cov.: 32

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.959

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.893

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.984

Gnomad OTH AF: 0.934

GnomAD4 exome AF: 0.964 AC: 17153 AN: 17802 Hom.: 8280 Cov.: 0 AF XY: 0.965 AC XY: 8803 AN XY: 9122

African (AFR) AF: 0.826 AC: 504 AN: 610

American (AMR) AF: 0.969 AC: 401 AN: 414

Ashkenazi Jewish (ASJ) AF: 0.923 AC: 698 AN: 756

East Asian (EAS) AF: 0.840 AC: 519 AN: 618

South Asian (SAS) AF: 0.902 AC: 702 AN: 778

European-Finnish (FIN) AF: 0.954 AC: 769 AN: 806

Middle Eastern (MID) AF: 0.951 AC: 97 AN: 102

European-Non Finnish (NFE) AF: 0.983 AC: 12269 AN: 12478

Other (OTH) AF: 0.963 AC: 1194 AN: 1240

GnomAD4 genome AF: 0.930 AC: 141508 AN: 152218 Hom.: 66122 Cov.: 32 AF XY: 0.927 AC XY: 68958 AN XY: 74412

African (AFR) AF: 0.836 AC: 34714 AN: 41516

American (AMR) AF: 0.959 AC: 14678 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3251 AN: 3470

East Asian (EAS) AF: 0.845 AC: 4331 AN: 5128

South Asian (SAS) AF: 0.893 AC: 4309 AN: 4826

European-Finnish (FIN) AF: 0.956 AC: 10155 AN: 10624

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.984 AC: 66938 AN: 68024

Other (OTH) AF: 0.935 AC: 1976 AN: 2114

Alfa AF: 0.958 Hom.: 103090

Bravo AF: 0.928

Asia WGS AF: 0.874 AC: 3041 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	-0.81
CADD	Benign	8.8
DANN	Benign	0.78
PhyloP100		0.044
PromoterAI		-0.081	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: rs2704505; hg19: chr10-71561770;