rs3024405

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000129.4(F13A1):​c.973+937A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,688 control chromosomes in the GnomAD database, including 16,698 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 0.46 ( 16698 hom., cov: 30)

Consequence

F13A1
NM_000129.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.09
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
F13A1NM_000129.4 linkuse as main transcriptc.973+937A>T intron_variant ENST00000264870.8 NP_000120.2 P00488

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
F13A1ENST00000264870.8 linkuse as main transcriptc.973+937A>T intron_variant 1 NM_000129.4 ENSP00000264870.3 P00488
F13A1ENST00000445223.1 linkuse as main transcriptc.121+937A>T intron_variant 2 ENSP00000394693.1 H0Y4W5

Frequencies

GnomAD3 genomes
AF:
0.458
AC:
69425
AN:
151572
Hom.:
16664
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.577
Gnomad AMI
AF:
0.380
Gnomad AMR
AF:
0.372
Gnomad ASJ
AF:
0.480
Gnomad EAS
AF:
0.652
Gnomad SAS
AF:
0.512
Gnomad FIN
AF:
0.410
Gnomad MID
AF:
0.618
Gnomad NFE
AF:
0.393
Gnomad OTH
AF:
0.461
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.458
AC:
69517
AN:
151688
Hom.:
16698
Cov.:
30
AF XY:
0.461
AC XY:
34118
AN XY:
74084
show subpopulations
Gnomad4 AFR
AF:
0.577
Gnomad4 AMR
AF:
0.372
Gnomad4 ASJ
AF:
0.480
Gnomad4 EAS
AF:
0.653
Gnomad4 SAS
AF:
0.513
Gnomad4 FIN
AF:
0.410
Gnomad4 NFE
AF:
0.393
Gnomad4 OTH
AF:
0.463
Alfa
AF:
0.412
Hom.:
1630
Bravo
AF:
0.455
Asia WGS
AF:
0.574
AC:
1994
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
7.5
DANN
Benign
0.71

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3024405; hg19: chr6-6223982; API