rs9328349

Variant names:

• chr6-6287395-T-G
• rs9328349
• NM_000129.4:c.319+17956A>C

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+17956A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0746 in 152,242 control chromosomes in the GnomAD database, including 1,109 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 0.075 (1109 hom., cov: 33)
• Consequence: F13A1 NM_000129.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.619
• Publications: 0 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F13A1	NM_000129.4	c.319+17956A>C		intron_variant	Intron 3 of 14	ENST00000264870.8	NP_000120.2
LOC124901253	XR_007059428.1	n.54+1455T>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F13A1	ENST00000264870.8	c.319+17956A>C		intron_variant	Intron 3 of 14	1	NM_000129.4	ENSP00000264870.3

Frequencies

GnomAD3 genomes AF: 0.0745 AC: 11328 AN: 152124 Hom.: 1106 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0324

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.0687

Gnomad SAS AF: 0.0864

Gnomad FIN AF: 0.00679

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00844

Gnomad OTH AF: 0.0506

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

GnomAD4 genome AF: 0.0746 AC: 11360 AN: 152242 Hom.: 1109 Cov.: 33 AF XY: 0.0744 AC XY: 5539 AN XY: 74438

African (AFR) AF: 0.223 AC: 9243 AN: 41518

American (AMR) AF: 0.0323 AC: 495 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0219 AC: 76 AN: 3470

East Asian (EAS) AF: 0.0687 AC: 355 AN: 5170

South Asian (SAS) AF: 0.0859 AC: 414 AN: 4820

European-Finnish (FIN) AF: 0.00679 AC: 72 AN: 10610

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00844 AC: 574 AN: 68028

Other (OTH) AF: 0.0548 AC: 116 AN: 2116

Alfa AF: 0.0396 Hom.: 106

Bravo AF: 0.0822

Asia WGS AF: 0.0880 AC: 304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.4
DANN	Benign	0.52
PhyloP100		0.62
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: rs9328349; hg19: chr6-6287628;