6-6222149-T-G

Position:

chr6-6222149-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000129.4(F13A1):c.996A>C(p.Pro332=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,613,808 control chromosomes in the GnomAD database, including 28,921 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2036 hom., cov: 32)

Exomes 𝑓: 0.19 ( 26885 hom. )

Consequence

F13A1
NM_000129.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0150

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 6-6222149-T-G is Benign according to our data. Variant chr6-6222149-T-G is described in ClinVar as [Benign]. Clinvar id is 255187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.015 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F13A1	NM_000129.4 linkuse as main transcript	c.996A>C	p.Pro332=	synonymous_variant	8/15	ENST00000264870.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F13A1	ENST00000264870.8 linkuse as main transcript	c.996A>C	p.Pro332=	synonymous_variant	8/15	1	NM_000129.4	P1
F13A1	ENST00000445223.1 linkuse as main transcript	c.147A>C	p.Pro49=	synonymous_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22901

AN:

152104

Hom.:

2032

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0841

Gnomad AMI

AF:

0.236

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.141

GnomAD3 exomes

AF:

0.154

AC:

38737

AN:

251024

Hom.:

3455

AF XY:

0.158

AC XY:

21494

AN XY:

135642

show subpopulations

Gnomad AFR exome

AF:

0.0819

Gnomad AMR exome

AF:

0.126

Gnomad ASJ exome

AF:

0.177

Gnomad EAS exome

AF:

0.00223

Gnomad SAS exome

AF:

0.134

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.195

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.187

AC:

272946

AN:

1461586

Hom.:

26885

Cov.:

AF XY:

0.186

AC XY:

135134

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.0770

Gnomad4 AMR exome

AF:

0.129

Gnomad4 ASJ exome

AF:

0.176

Gnomad4 EAS exome

AF:

0.000983

Gnomad4 SAS exome

AF:

0.135

Gnomad4 FIN exome

AF:

0.184

Gnomad4 NFE exome

AF:

0.205

Gnomad4 OTH exome

AF:

0.171

GnomAD4 genome

AF:

0.151

AC:

22915

AN:

152222

Hom.:

2036

Cov.:

AF XY:

0.146

AC XY:

10828

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0843

Gnomad4 AMR

AF:

0.131

Gnomad4 ASJ

AF:

0.170

Gnomad4 EAS

AF:

0.00308

Gnomad4 SAS

AF:

0.132

Gnomad4 FIN

AF:

0.193

Gnomad4 NFE

AF:

0.200

Gnomad4 OTH

AF:

0.139

Alfa

AF:

0.178

Hom.:

1441

Bravo

AF:

0.144

Asia WGS

AF:

0.0600

AC:

209

AN:

3478

EpiCase

AF:

0.195

EpiControl

AF:

0.199

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Factor XIII, A subunit, deficiency of

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.3

DANN

Benign

0.79

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over