8-17868600-T-A

Position:

• chr8-17868600-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_004467.4(FGL1):​c.727A>T​(p.Asn243Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FGL1 NM_004467.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.98

Genes affected

FGL1 (HGNC:3695): (fibrinogen like 1) Fibrinogen-like 1 is a member of the fibrinogen family. This protein is homologous to the carboxy terminus of the fibrinogen beta- and gamma- subunits which contains the four conserved cysteines of fibrinogens and fibrinogen related proteins. However, this protein lacks the platelet-binding site, cross-linking region and a thrombin-sensitive site which are necessary for fibrin clot formation. This protein may play a role in the development of hepatocellular carcinomas. Four alternatively spliced transcript variants encoding the same protein exist for this gene. [provided by RefSeq, Jul 2008]

FGL1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.806

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGL1	NM_004467.4	c.727A>T	p.Asn243Tyr	missense_variant	7/8	ENST00000427924.5	NP_004458.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGL1	ENST00000427924.5	c.727A>T	p.Asn243Tyr	missense_variant	7/8	1	NM_004467.4	ENSP00000401952.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 09, 2024

The c.727A>T (p.N243Y) alteration is located in exon 8 (coding exon 6) of the FGL1 gene. This alteration results from a A to T substitution at nucleotide position 727, causing the asparagine (N) at amino acid position 243 to be replaced by a tyrosine (Y). 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	0.12
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.020	T;T;T;T;T;T;T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.91	.;.;.;.;.;D;.
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.81	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Uncertain	2.3	M;M;M;M;M;M;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.7	D;D;D;D;D;D;D
REVEL	Uncertain	0.46
Sift	Benign	0.052	T;T;T;T;T;T;T
Sift4G	Uncertain	0.052	T;T;T;T;T;T;T
Polyphen		1.0	D;D;D;D;D;D;D
Vest4		0.67
MutPred		0.38		Gain of phosphorylation at N243 (P = 0.0264);Gain of phosphorylation at N243 (P = 0.0264);Gain of phosphorylation at N243 (P = 0.0264);Gain of phosphorylation at N243 (P = 0.0264);Gain of phosphorylation at N243 (P = 0.0264);Gain of phosphorylation at N243 (P = 0.0264);Gain of phosphorylation at N243 (P = 0.0264);
MVP		0.75
ClinPred		0.99	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.25
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-17726109;