NM_000129.4:c.-19+12A>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000129.4(F13A1):c.-19+12A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 466,414 control chromosomes in the GnomAD database, including 177,234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59146 hom., cov: 33)

Exomes 𝑓: 0.87 ( 118088 hom. )

Consequence

F13A1
NM_000129.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.36

Publications

13 publications found

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]

F13A1 Gene-Disease associations (from GenCC):

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

F13A1 links:

ENSG00000309672 (HGNC:):

ENSG00000309672 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-6320575-T-G is Benign according to our data. Variant chr6-6320575-T-G is described in ClinVar as Benign. ClinVar VariationId is 357680.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F13A1	NM_000129.4	MANE Select	c.-19+12A>C		intron	N/A	NP_000120.2	P00488

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
F13A1	ENST00000264870.8	TSL:1 MANE Select	c.-19+12A>C	intron	N/A	ENSP00000264870.3	P00488
F13A1	ENST00000878383.1		c.-19+12A>C	intron	N/A	ENSP00000548442.1
F13A1	ENST00000950946.1		c.-19+12A>C	intron	N/A	ENSP00000621005.1

Frequencies

GnomAD3 genomes

AF:

0.881

AC:

134043

AN:

152090

Hom.:

59096

Cov.:

show subpopulations

Gnomad AFR

AF:

0.890

Gnomad AMI

AF:

0.863

Gnomad AMR

AF:

0.866

Gnomad ASJ

AF:

0.855

Gnomad EAS

AF:

0.956

Gnomad SAS

AF:

0.795

Gnomad FIN

AF:

0.854

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.887

Gnomad OTH

AF:

0.872

GnomAD2 exomes

AF:

0.870

AC:

125895

AN:

144754

AF XY:

0.866

show subpopulations

Gnomad AFR exome

AF:

0.892

Gnomad AMR exome

AF:

0.857

Gnomad ASJ exome

AF:

0.858

Gnomad EAS exome

AF:

0.954

Gnomad FIN exome

AF:

0.860

Gnomad NFE exome

AF:

0.894

Gnomad OTH exome

AF:

0.860

GnomAD4 exome

AF:

0.866

AC:

271953

AN:

314206

Hom.:

118088

Cov.:

AF XY:

0.859

AC XY:

152366

AN XY:

177384

show subpopulations

African (AFR)

AF:

0.889

AC:

7590

AN:

8534

American (AMR)

AF:

0.857

AC:

22979

AN:

26808

Ashkenazi Jewish (ASJ)

AF:

0.854

AC:

8929

AN:

10458

East Asian (EAS)

AF:

0.956

AC:

8783

AN:

9186

South Asian (SAS)

AF:

0.792

AC:

46743

AN:

59002

European-Finnish (FIN)

AF:

0.862

AC:

23157

AN:

26876

Middle Eastern (MID)

AF:

0.819

AC:

2258

AN:

2756

European-Non Finnish (NFE)

AF:

0.890

AC:

139242

AN:

156486

Other (OTH)

AF:

0.870

AC:

12272

AN:

14100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1958

3916

5874

7832

9790

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

638

1276

1914

2552

3190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.881

AC:

134148

AN:

152208

Hom.:

59146

Cov.:

AF XY:

0.879

AC XY:

65428

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.890

AC:

36955

AN:

41528

American (AMR)

AF:

0.866

AC:

13245

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.855

AC:

2968

AN:

3472

East Asian (EAS)

AF:

0.956

AC:

4921

AN:

5150

South Asian (SAS)

AF:

0.795

AC:

3832

AN:

4818

European-Finnish (FIN)

AF:

0.854

AC:

9070

AN:

10620

Middle Eastern (MID)

AF:

0.799

AC:

235

AN:

294

European-Non Finnish (NFE)

AF:

0.887

AC:

60299

AN:

68004

Other (OTH)

AF:

0.869

AC:

1838

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

826

1652

2478

3304

4130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.883

Hom.:

98483

Bravo

AF:

0.887

Asia WGS

AF:

0.838

AC:

2915

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Factor XIII, A subunit, deficiency of (2)

not specified (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

(source)

DANN

Benign

0.34

PhyloP100

-3.4

PromoterAI

-0.13

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over