1-197040569-T-A

Variant names:

• chr1-197040569-T-A
• NM_001994.3:c.1905A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001994.3(F13B):​c.1905A>T​(p.Gln635His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: F13B NM_001994.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.12
• Publications: 0 publications found

Genes affected

F13B (HGNC:3534): (coagulation factor XIII B chain) This gene encodes coagulation factor XIII B 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 a plasma carrier molecules. Platelet factor XIII is comprised only of 2 A subunits, which are identical to those of plasma origin. Upon activation by the 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. 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]

F13B Gene-Disease associations (from GenCC):

• factor XIII, b subunit, deficiency of

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• congenital factor XIII deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F13B	NM_001994.3	c.1905A>T	p.Gln635His	missense_variant	Exon 11 of 12	ENST00000367412.2	NP_001985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F13B	ENST00000367412.2	c.1905A>T	p.Gln635His	missense_variant	Exon 11 of 12	1	NM_001994.3	ENSP00000356382.2
F13B	ENST00000649282.1	c.660A>T	p.Gln220His	missense_variant	Exon 4 of 5			ENSP00000497116.1
F13B	ENST00000490002.1	n.316A>T		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Apr 11, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1905A>T (p.Q635H) alteration is located in exon 11 (coding exon 11) of the F13B gene. This alteration results from a A to T substitution at nucleotide position 1905, causing the glutamine (Q) at amino acid position 635 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	0.0080
DANN	Benign	0.89
DEOGEN2	Uncertain	0.51	.;D
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Pathogenic	3.0	.;M
PhyloP100		-3.1
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.5	.;N
REVEL	Uncertain	0.48
Sift	Uncertain	0.0050	.;D
Sift4G	Uncertain	0.015	.;D
Polyphen		0.94	.;P
Vest4		0.46
MutPred		0.51		.;Gain of catalytic residue at Q635 (P = 0.0531);
MVP		0.73
MPC		0.44
ClinPred		0.78	D
GERP RS		-7.3
Varity_R		0.13
gMVP		0.68
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr1-197009699;