rs3024388

Variant names:

• chr6-6249412-C-T
• rs3024388
• NM_000129.4:c.691-993G>A

Variant summary

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

The NM_000129.4(F13A1):​c.691-993G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,160 control chromosomes in the GnomAD database, including 4,856 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 0.24 (4856 hom., cov: 33)
• Consequence: F13A1 NM_000129.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 5 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.416 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.691-993G>A		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.691-993G>A		intron	N/A	ENSP00000264870.3

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37071 AN: 152042 Hom.: 4854 Cov.: 33

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.244 AC: 37079 AN: 152160 Hom.: 4856 Cov.: 33 AF XY: 0.250 AC XY: 18573 AN XY: 74376

African (AFR) AF: 0.176 AC: 7296 AN: 41528

American (AMR) AF: 0.250 AC: 3828 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 790 AN: 3468

East Asian (EAS) AF: 0.425 AC: 2191 AN: 5158

South Asian (SAS) AF: 0.431 AC: 2080 AN: 4824

European-Finnish (FIN) AF: 0.293 AC: 3097 AN: 10576

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16883 AN: 68000

Other (OTH) AF: 0.261 AC: 551 AN: 2110

Alfa AF: 0.251 Hom.: 8038

Bravo AF: 0.237

Asia WGS AF: 0.443 AC: 1539 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.48
PhyloP100		-1.3
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: rs3024388; hg19: chr6-6249645;