rs11243069

Variant names:

• chr6-6289770-G-A
• rs11243069
• NM_000129.4:c.319+15581C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000129.4(F13A1):​c.319+15581C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0833 in 151,756 control chromosomes in the GnomAD database, including 682 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 0.083 (682 hom., cov: 32)
• Consequence: F13A1 NM_000129.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336
• Publications: 3 publications found

Genes affected

F13A1 (HGNC:3531): (coagulation factor XIII A chain) This gene encodes the coagulation factor XIII A subunit. Coagulation factor XIII is the last zymogen to become activated in the blood coagulation cascade. Plasma factor XIII is a heterotetramer composed of 2 A subunits and 2 B subunits. The A subunits have catalytic function, and the B subunits do not have enzymatic activity and may serve as plasma carrier molecules. Platelet factor XIII is comprised only of 2 A subunits, which are identical to those of plasma origin. Upon cleavage of the activation peptide by thrombin and in the presence of calcium ion, the plasma factor XIII dissociates its B subunits and yields the same active enzyme, factor XIIIa, as platelet factor XIII. This enzyme acts as a transglutaminase to catalyze the formation of gamma-glutamyl-epsilon-lysine crosslinking between fibrin molecules, thus stabilizing the fibrin clot. It also crosslinks alpha-2-plasmin inhibitor, or fibronectin, to the alpha chains of fibrin. Factor XIII deficiency is classified into two categories: type I deficiency, characterized by the lack of both the A and B subunits; and type II deficiency, characterized by the lack of the A subunit alone. These defects can result in a lifelong bleeding tendency, defective wound healing, and habitual abortion. [provided by RefSeq, Jul 2008]

F13A1 Gene-Disease associations (from GenCC):

• factor XIII, A subunit, deficiency of

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen
• congenital factor XIII deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000309672 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F13A1	NM_000129.4	c.319+15581C>T		intron_variant	Intron 3 of 14	ENST00000264870.8	NP_000120.2
LOC124901253	XR_007059428.1	n.54+3830G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F13A1	ENST00000264870.8	c.319+15581C>T		intron_variant	Intron 3 of 14	1	NM_000129.4	ENSP00000264870.3

Frequencies

GnomAD3 genomes AF: 0.0833 AC: 12637 AN: 151654 Hom.: 683 Cov.: 32

Gnomad AFR AF: 0.0212

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0690

Gnomad FIN AF: 0.0925

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0833 AC: 12634 AN: 151756 Hom.: 682 Cov.: 32 AF XY: 0.0828 AC XY: 6138 AN XY: 74158

African (AFR) AF: 0.0211 AC: 873 AN: 41366

American (AMR) AF: 0.133 AC: 2031 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 392 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5186

South Asian (SAS) AF: 0.0697 AC: 335 AN: 4808

European-Finnish (FIN) AF: 0.0925 AC: 965 AN: 10430

Middle Eastern (MID) AF: 0.138 AC: 40 AN: 290

European-Non Finnish (NFE) AF: 0.112 AC: 7594 AN: 67956

Other (OTH) AF: 0.100 AC: 211 AN: 2106

Alfa AF: 0.106 Hom.: 1482

Bravo AF: 0.0836

Asia WGS AF: 0.0350 AC: 124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.73
DANN	Benign	0.75
PhyloP100		-0.34
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: rs11243069; hg19: chr6-6290003;