chr6-6182372-C-T

Position:

• chr6-6182372-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F13A1	NM_000129.4	c.1306-231G>A		intron_variant		ENST00000264870.8	NP_000120.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F13A1	ENST00000264870.8	c.1306-231G>A		intron_variant		1	NM_000129.4	ENSP00000264870.3

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

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.315

Alfa AF: 0.249 Hom.: 6794

Bravo AF: 0.326

Asia WGS AF: 0.450 AC: 1563 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.24
DANN	Benign	0.40

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

LitVar

Other links and lift over

dbSNP: rs2274393; hg19: chr6-6182605;