NM_000129.4:c.1306-231G>A

Variant names:

• chr6-6182372-C-T
• rs2274393
• NM_000129.4:c.1306-231G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000129.4(F13A1):​c.1306-231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,986 control chromosomes in the GnomAD database, including 8,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (8437 hom., cov: 32)
• Consequence: F13A1 NM_000129.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.757
• Publications: 11 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 6-6182372-C-T is Benign according to our data. Variant chr6-6182372-C-T is described in ClinVar as Benign. ClinVar VariationId is 1226969.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.508 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.1306-231G>A		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.1306-231G>A		intron	N/A	ENSP00000264870.3	P00488
	F13A1	ENST00000950947.1		c.1306-231G>A		intron	N/A	ENSP00000621006.1
	F13A1	ENST00000878383.1		c.1117-231G>A		intron	N/A	ENSP00000548442.1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47722 AN: 151866 Hom.: 8421 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.314 AC: 47775 AN: 151986 Hom.: 8437 Cov.: 32 AF XY: 0.321 AC XY: 23857 AN XY: 74296

African (AFR) AF: 0.446 AC: 18478 AN: 41418

American (AMR) AF: 0.331 AC: 5057 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3472

East Asian (EAS) AF: 0.525 AC: 2710 AN: 5164

South Asian (SAS) AF: 0.406 AC: 1951 AN: 4810

European-Finnish (FIN) AF: 0.258 AC: 2725 AN: 10568

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14919 AN: 67964

Other (OTH) AF: 0.315 AC: 664 AN: 2108

Alfa AF: 0.258 Hom.: 10247

Bravo AF: 0.326

Asia WGS AF: 0.450 AC: 1563 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.24
DANN	Benign	0.40
PhyloP100		-0.76
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: rs2274393; hg19: chr6-6182605;