6-6222149-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000129.4(F13A1):c.996A>C(p.Pro332Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,613,808 control chromosomes in the GnomAD database, including 28,921 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2036 hom., cov: 32)

Exomes 𝑓: 0.19 ( 26885 hom. )

Consequence

F13A1
NM_000129.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0150

Publications

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

F13A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.077).

BP6

Variant 6-6222149-T-G is Benign according to our data. Variant chr6-6222149-T-G is described in ClinVar as Benign. ClinVar VariationId is 255187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.015 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 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.996A>C	p.Pro332Pro	synonymous	Exon 8 of 15	NP_000120.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
F13A1	ENST00000264870.8	TSL:1 MANE Select	c.996A>C	p.Pro332Pro	synonymous	Exon 8 of 15	ENSP00000264870.3
F13A1	ENST00000950947.1		c.996A>C	p.Pro332Pro	synonymous	Exon 7 of 14	ENSP00000621006.1
F13A1	ENST00000878383.1		c.807A>C	p.Pro269Pro	synonymous	Exon 7 of 14	ENSP00000548442.1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22901

AN:

152104

Hom.:

2032

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0841

Gnomad AMI

AF:

0.236

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.141

GnomAD2 exomes

AF:

0.154

AC:

38737

AN:

251024

AF XY:

0.158

show subpopulations

Gnomad AFR exome

AF:

0.0819

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.00223

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.195

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.187

AC:

272946

AN:

1461586

Hom.:

26885

Cov.:

AF XY:

0.186

AC XY:

135134

AN XY:

727110

show subpopulations

African (AFR)

AF:

0.0770

AC:

2578

AN:

33472

American (AMR)

AF:

0.129

AC:

5774

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

4603

AN:

26124

East Asian (EAS)

AF:

0.000983

AC:

AN:

39684

South Asian (SAS)

AF:

0.135

AC:

11656

AN:

86254

European-Finnish (FIN)

AF:

0.184

AC:

9806

AN:

53406

Middle Eastern (MID)

AF:

0.112

AC:

645

AN:

5768

European-Non Finnish (NFE)

AF:

0.205

AC:

227497

AN:

1111780

Other (OTH)

AF:

0.171

AC:

10348

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

12119

24239

36358

48478

60597

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7804

15608

23412

31216

39020

<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:

0.151

AC:

22915

AN:

152222

Hom.:

2036

Cov.:

AF XY:

0.146

AC XY:

10828

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.0843

AC:

3502

AN:

41548

American (AMR)

AF:

0.131

AC:

1997

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

591

AN:

3468

East Asian (EAS)

AF:

0.00308

AC:

AN:

5190

South Asian (SAS)

AF:

0.132

AC:

636

AN:

4822

European-Finnish (FIN)

AF:

0.193

AC:

2044

AN:

10606

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.200

AC:

13595

AN:

67976

Other (OTH)

AF:

0.139

AC:

293

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

980

1961

2941

3922

4902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

254

508

762

1016

1270

<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:

0.177

Hom.:

1444

Bravo

AF:

0.144

Asia WGS

AF:

0.0600

AC:

209

AN:

3478

EpiCase

AF:

0.195

EpiControl

AF:

0.199

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Factor XIII, A subunit, deficiency of (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.3

(source)

DANN

Benign

0.79

PhyloP100

-0.015

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