NM_000129.4:c.*443G>A

Variant names:

• chr6-6145176-C-T
• rs3024486
• NM_000129.4:c.*443G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000129.4(F13A1):​c.*443G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0497 in 215,478 control chromosomes in the GnomAD database, including 374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.048 (239 hom., cov: 32)
  • Exomes 𝑓: 0.055 (135 hom.)
• Consequence: F13A1 NM_000129.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.645
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-6145176-C-T is Benign according to our data. Variant chr6-6145176-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 357658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0688 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.*443G>A		3_prime_UTR	Exon 15 of 15	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.*443G>A		3_prime_UTR	Exon 15 of 15	ENSP00000264870.3	P00488
	F13A1	ENST00000950947.1		c.*443G>A		3_prime_UTR	Exon 14 of 14	ENSP00000621006.1
	F13A1	ENST00000878383.1		c.*443G>A		3_prime_UTR	Exon 14 of 14	ENSP00000548442.1

Frequencies

GnomAD3 genomes AF: 0.0477 AC: 7248 AN: 151996 Hom.: 238 Cov.: 32

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0492

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.0197

Gnomad SAS AF: 0.0260

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0705

Gnomad OTH AF: 0.0561

GnomAD4 exome AF: 0.0547 AC: 3463 AN: 63364 Hom.: 135 Cov.: 0 AF XY: 0.0522 AC XY: 1756 AN XY: 33670

African (AFR) AF: 0.00917 AC: 12 AN: 1308

American (AMR) AF: 0.0313 AC: 114 AN: 3640

Ashkenazi Jewish (ASJ) AF: 0.0410 AC: 54 AN: 1318

East Asian (EAS) AF: 0.0190 AC: 54 AN: 2840

South Asian (SAS) AF: 0.0277 AC: 253 AN: 9136

European-Finnish (FIN) AF: 0.0601 AC: 193 AN: 3210

Middle Eastern (MID) AF: 0.0588 AC: 14 AN: 238

European-Non Finnish (NFE) AF: 0.0672 AC: 2579 AN: 38396

Other (OTH) AF: 0.0580 AC: 190 AN: 3278

GnomAD4 genome AF: 0.0476 AC: 7245 AN: 152114 Hom.: 239 Cov.: 32 AF XY: 0.0459 AC XY: 3412 AN XY: 74344

African (AFR) AF: 0.0125 AC: 520 AN: 41500

American (AMR) AF: 0.0491 AC: 750 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3470

East Asian (EAS) AF: 0.0197 AC: 102 AN: 5176

South Asian (SAS) AF: 0.0260 AC: 125 AN: 4802

European-Finnish (FIN) AF: 0.0548 AC: 580 AN: 10592

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0705 AC: 4792 AN: 67996

Other (OTH) AF: 0.0555 AC: 117 AN: 2108

Alfa AF: 0.0636 Hom.: 577

Bravo AF: 0.0471

Asia WGS AF: 0.0240 AC: 83 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Factor XIII, A subunit, deficiency of (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.30
PhyloP100		-0.65
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: rs3024486; hg19: chr6-6145409;