chr6-6288009-A-G

Variant names:

• chr6-6288009-A-G
• rs12194855
• NM_000129.4:c.319+17342T>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+17342T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 151,864 control chromosomes in the GnomAD database, including 686 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 (686 hom., cov: 32)
• Consequence: F13A1 NM_000129.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000129.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F13A1	NM_000129.4	MANE Select	c.319+17342T>C		intron	N/A	NP_000120.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F13A1	ENST00000264870.8	TSL:1 MANE Select	c.319+17342T>C		intron	N/A	ENSP00000264870.3
	F13A1	ENST00000431222.6	TSL:4	c.481+17342T>C		intron	N/A	ENSP00000416295.2
	F13A1	ENST00000414279.5	TSL:4	c.319+17342T>C		intron	N/A	ENSP00000413334.1

Frequencies

GnomAD3 genomes AF: 0.0835 AC: 12674 AN: 151746 Hom.: 687 Cov.: 32

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0690

Gnomad FIN AF: 0.0924

Gnomad MID AF: 0.136

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: 0.0834 AC: 12670 AN: 151864 Hom.: 686 Cov.: 32 AF XY: 0.0831 AC XY: 6169 AN XY: 74238

African (AFR) AF: 0.0212 AC: 876 AN: 41398

American (AMR) AF: 0.134 AC: 2043 AN: 15216

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

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5152

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

European-Finnish (FIN) AF: 0.0924 AC: 979 AN: 10592

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7601 AN: 67922

Other (OTH) AF: 0.100 AC: 211 AN: 2104

Alfa AF: 0.0262 Hom.: 25

Bravo AF: 0.0836

Asia WGS AF: 0.0350 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.47
PhyloP100		0.15
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: rs12194855; hg19: chr6-6288242;