rs5987

Positions:

chr6-6151907-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000129.4(F13A1):c.1951G>A(p.Val651Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 1,613,824 control chromosomes in the GnomAD database, including 3,289 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 292 hom., cov: 33)

Exomes 𝑓: 0.061 ( 2997 hom. )

Consequence

F13A1
NM_000129.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.69

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002224654).

BP6

Variant 6-6151907-C-T is Benign according to our data. Variant chr6-6151907-C-T is described in ClinVar as [Benign]. Clinvar id is 255185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-6151907-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 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.1951G>A	p.Val651Ile	missense_variant	14/15	ENST00000264870.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F13A1	ENST00000264870.8 linkuse as main transcript	c.1951G>A	p.Val651Ile	missense_variant	14/15	1	NM_000129.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0552

AC:

8397

AN:

152120

Hom.:

292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0359

Gnomad AMI

AF:

0.0615

Gnomad AMR

AF:

0.0583

Gnomad ASJ

AF:

0.0631

Gnomad EAS

AF:

0.100

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.0639

Gnomad MID

AF:

0.0892

Gnomad NFE

AF:

0.0562

Gnomad OTH

AF:

0.0574

GnomAD3 exomes

AF:

0.0659

AC:

16537

AN:

250912

Hom.:

642

AF XY:

0.0698

AC XY:

9460

AN XY:

135592

show subpopulations

Gnomad AFR exome

AF:

0.0355

Gnomad AMR exome

AF:

0.0465

Gnomad ASJ exome

AF:

0.0704

Gnomad EAS exome

AF:

0.0956

Gnomad SAS exome

AF:

0.118

Gnomad FIN exome

AF:

0.0588

Gnomad NFE exome

AF:

0.0582

Gnomad OTH exome

AF:

0.0655

GnomAD4 exome

AF:

0.0605

AC:

88496

AN:

1461586

Hom.:

2997

Cov.:

AF XY:

0.0623

AC XY:

45289

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.0362

Gnomad4 AMR exome

AF:

0.0468

Gnomad4 ASJ exome

AF:

0.0683

Gnomad4 EAS exome

AF:

0.111

Gnomad4 SAS exome

AF:

0.116

Gnomad4 FIN exome

AF:

0.0577

Gnomad4 NFE exome

AF:

0.0556

Gnomad4 OTH exome

AF:

0.0603

GnomAD4 genome

AF:

0.0552

AC:

8401

AN:

152238

Hom.:

292

Cov.:

AF XY:

0.0576

AC XY:

4287

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0359

Gnomad4 AMR

AF:

0.0582

Gnomad4 ASJ

AF:

0.0631

Gnomad4 EAS

AF:

0.100

Gnomad4 SAS

AF:

0.119

Gnomad4 FIN

AF:

0.0639

Gnomad4 NFE

AF:

0.0562

Gnomad4 OTH

AF:

0.0587

Alfa

AF:

0.0587

Hom.:

286

Bravo

AF:

0.0522

TwinsUK

AF:

0.0483

AC:

179

ALSPAC

AF:

0.0594

AC:

229

ESP6500AA

AF:

0.0304

AC:

134

ESP6500EA

AF:

0.0593

AC:

510

ExAC

AF:

0.0675

AC:

8195

Asia WGS

AF:

0.0960

AC:

334

AN:

3478

EpiCase

AF:

0.0630

EpiControl

AF:

0.0620

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 13, 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

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.49

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.056

FATHMM_MKL

Benign

0.48

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.00022

PrimateAI

Benign

0.37

PROVEAN

Benign

0.020

REVEL

Benign

0.16

Sift

Benign

0.87

Sift4G

Benign

0.84

Vest4

0.18

MPC

0.18

ClinPred

0.023

GERP RS

5.4

gMVP

0.47

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