chr6-6145459-C-T

Variant names:

• chr6-6145459-C-T
• rs1050783
• NM_000129.4:c.*160G>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.*160G>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 0.16 in 882,710 control chromosomes in the GnomAD database, including 12,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2723 hom., cov: 32)
  • Exomes 𝑓: 0.16 (9884 hom.)
• Consequence: F13A1 NM_000129.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.801
• Publications: 12 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=-0.89).
• BP6: Variant 6-6145459-C-T is Benign according to our data. Variant chr6-6145459-C-T is described in ClinVar as Benign. ClinVar VariationId is 357662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 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.*160G>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.*160G>A		3_prime_UTR	Exon 15 of 15	ENSP00000264870.3	P00488
	F13A1	ENST00000950947.1		c.*160G>A		3_prime_UTR	Exon 14 of 14	ENSP00000621006.1
	F13A1	ENST00000878383.1		c.*160G>A		3_prime_UTR	Exon 14 of 14	ENSP00000548442.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27309 AN: 152052 Hom.: 2706 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0878

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.182

GnomAD4 exome AF: 0.156 AC: 114230 AN: 730540 Hom.: 9884 Cov.: 10 AF XY: 0.153 AC XY: 58595 AN XY: 382342

African (AFR) AF: 0.251 AC: 4738 AN: 18888

American (AMR) AF: 0.166 AC: 5599 AN: 33764

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 4179 AN: 20156

East Asian (EAS) AF: 0.000270 AC: 9 AN: 33294

South Asian (SAS) AF: 0.0981 AC: 6326 AN: 64472

European-Finnish (FIN) AF: 0.118 AC: 4778 AN: 40434

Middle Eastern (MID) AF: 0.218 AC: 911 AN: 4176

European-Non Finnish (NFE) AF: 0.171 AC: 81825 AN: 479348

Other (OTH) AF: 0.163 AC: 5865 AN: 36008

GnomAD4 genome AF: 0.180 AC: 27357 AN: 152170 Hom.: 2723 Cov.: 32 AF XY: 0.174 AC XY: 12935 AN XY: 74394

African (AFR) AF: 0.248 AC: 10299 AN: 41500

American (AMR) AF: 0.162 AC: 2480 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 699 AN: 3472

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5186

South Asian (SAS) AF: 0.0877 AC: 422 AN: 4814

European-Finnish (FIN) AF: 0.129 AC: 1364 AN: 10588

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11586 AN: 67996

Other (OTH) AF: 0.180 AC: 380 AN: 2110

Alfa AF: 0.175 Hom.: 4098

Bravo AF: 0.186

Asia WGS AF: 0.0520 AC: 184 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-0.89
CADD	Benign	0.50
DANN	Benign	0.31
PhyloP100		-0.80
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: rs1050783; hg19: chr6-6145692;