6-6172447-T-C

Variant names:

• chr6-6172447-T-C
• rs387528
• NM_000129.4:c.1747+2133A>G

Variant summary

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

The NM_000129.4(F13A1):​c.1747+2133A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 150,182 control chromosomes in the GnomAD database, including 33,188 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 0.65 (33188 hom., cov: 28)
• Consequence: F13A1 NM_000129.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.882
• 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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.809 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.1747+2133A>G		intron	N/A	NP_000120.2	P00488

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F13A1	ENST00000264870.8	TSL:1 MANE Select	c.1747+2133A>G		intron	N/A	ENSP00000264870.3	P00488
	F13A1	ENST00000950947.1		c.1747+2133A>G		intron	N/A	ENSP00000621006.1
	F13A1	ENST00000878383.1		c.1558+2133A>G		intron	N/A	ENSP00000548442.1

Frequencies

GnomAD3 genomes AF: 0.655 AC: 98234 AN: 150080 Hom.: 33141 Cov.: 28

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.586

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.777

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.655 AC: 98324 AN: 150182 Hom.: 33188 Cov.: 28 AF XY: 0.658 AC XY: 48152 AN XY: 73224

African (AFR) AF: 0.816 AC: 33311 AN: 40820

American (AMR) AF: 0.510 AC: 7727 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2283 AN: 3462

East Asian (EAS) AF: 0.601 AC: 3041 AN: 5064

South Asian (SAS) AF: 0.709 AC: 3374 AN: 4758

European-Finnish (FIN) AF: 0.666 AC: 6726 AN: 10106

Middle Eastern (MID) AF: 0.781 AC: 228 AN: 292

European-Non Finnish (NFE) AF: 0.588 AC: 39719 AN: 67532

Other (OTH) AF: 0.665 AC: 1384 AN: 2082

Alfa AF: 0.602 Hom.: 101401

Bravo AF: 0.646

Asia WGS AF: 0.664 AC: 2268 AN: 3414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.49
PhyloP100		0.88
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: rs387528; hg19: chr6-6172680;