rs3024480

Positions:

• chr6-6222016-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000129.4(F13A1):​c.1112+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00827 in 1,612,940 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (33 hom., cov: 32)
  • Exomes 𝑓: 0.0077 (81 hom.)
• Consequence: F13A1 NM_000129.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.549

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=-0.82).
• BP6: Variant 6-6222016-T-C is Benign according to our data. Variant chr6-6222016-T-C is described in ClinVar as [Benign]. Clinvar id is 255182.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0133 (2023/152308) while in subpopulation AFR AF= 0.0262 (1089/41558). AF 95% confidence interval is 0.0249. There are 33 homozygotes in gnomad4. There are 966 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F13A1	NM_000129.4	c.1112+17A>G		intron_variant		ENST00000264870.8	NP_000120.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F13A1	ENST00000264870.8	c.1112+17A>G		intron_variant		1	NM_000129.4	ENSP00000264870.3
F13A1	ENST00000445223.1	c.260+17A>G		intron_variant		2		ENSP00000394693.1

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 2009 AN: 152190 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.0260

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00704

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00858

Gnomad OTH AF: 0.0163

GnomAD3 exomes AF: 0.00892 AC: 2233 AN: 250316 Hom.: 23 AF XY: 0.00901 AC XY: 1219 AN XY: 135334

Gnomad AFR exome AF: 0.0265

Gnomad AMR exome AF: 0.00750

Gnomad ASJ exome AF: 0.0218

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00833

Gnomad FIN exome AF: 0.000993

Gnomad NFE exome AF: 0.00867

Gnomad OTH exome AF: 0.0106

GnomAD4 exome AF: 0.00774 AC: 11308 AN: 1460632 Hom.: 81 Cov.: 31 AF XY: 0.00790 AC XY: 5744 AN XY: 726684

Gnomad4 AFR exome AF: 0.0252

Gnomad4 AMR exome AF: 0.00807

Gnomad4 ASJ exome AF: 0.0202

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00835

Gnomad4 FIN exome AF: 0.00134

Gnomad4 NFE exome AF: 0.00702

Gnomad4 OTH exome AF: 0.0114

GnomAD4 genome AF: 0.0133 AC: 2023 AN: 152308 Hom.: 33 Cov.: 32 AF XY: 0.0130 AC XY: 966 AN XY: 74484

Gnomad4 AFR AF: 0.0262

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.0236

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00725

Gnomad4 FIN AF: 0.000941

Gnomad4 NFE AF: 0.00859

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0127 Hom.: 4

Bravo AF: 0.0140

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.4
DANN	Benign	0.62

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: rs3024480; hg19: chr6-6222249;