chr6-6320575-T-A

Variant names:

• chr6-6320575-T-A
• rs2815822
• NM_000129.4:c.-19+12A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000129.4(F13A1):​c.-19+12A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000636 in 314,290 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: F13A1 NM_000129.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.36
• Publications: 13 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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen
• congenital factor XIII deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000309672 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F13A1	NM_000129.4	c.-19+12A>T		intron_variant	Intron 1 of 14	ENST00000264870.8	NP_000120.2
LOC124901253	XR_007059428.1	n.55-9178T>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F13A1	ENST00000264870.8	c.-19+12A>T		intron_variant	Intron 1 of 14	1	NM_000129.4	ENSP00000264870.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000691 AC: 1 AN: 144754 AF XY: 0.0000129

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000636 AC: 2 AN: 314290 Hom.: 0 Cov.: 0 AF XY: 0.0000113 AC XY: 2 AN XY: 177438

African (AFR) AF: 0.00 AC: 0 AN: 8538

American (AMR) AF: 0.00 AC: 0 AN: 26818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10462

East Asian (EAS) AF: 0.00 AC: 0 AN: 9186

South Asian (SAS) AF: 0.0000339 AC: 2 AN: 59022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 156524

Other (OTH) AF: 0.00 AC: 0 AN: 14102

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.17
PhyloP100		-3.4
PromoterAI		-0.11	Neutral

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: rs2815822; hg19: chr6-6320808;