NM_021870.3:c.418T>G

Variant names:

• chr4-154610181-A-C
• NM_021870.3:c.418T>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021870.3(FGG):​c.418T>G​(p.Tyr140Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,431,872 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: FGG NM_021870.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81

Genes affected

FGG (HGNC:3694): (fibrinogen gamma chain) The protein encoded by this gene is the gamma component of fibrinogen, a blood-borne glycoprotein comprised of three pairs of nonidentical polypeptide chains. Following vascular injury, fibrinogen is cleaved by thrombin to form fibrin which is the most abundant component of blood clots. In addition, various cleavage products of fibrinogen and fibrin regulate cell adhesion and spreading, display vasoconstrictor and chemotactic activities, and are mitogens for several cell types. Mutations in this gene lead to several disorders, including dysfibrinogenemia, hypofibrinogenemia and thrombophilia. Alternative splicing results in transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
FGG	NM_021870.3	c.418T>G	p.Tyr140Asp	missense_variant	Exon 5 of 9	ENST00000336098.8	NP_068656.2
FGG	NM_000509.6	c.418T>G	p.Tyr140Asp	missense_variant	Exon 5 of 10		NP_000500.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGG	ENST00000336098.8	c.418T>G	p.Tyr140Asp	missense_variant	Exon 5 of 9	2	NM_021870.3	ENSP00000336829.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1431872 Hom.: 0 Cov.: 28 AF XY: 0.00000140 AC XY: 1 AN XY: 714284

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.22e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Uncertain	0.57	.;.;D;T;T;T
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.76	T;T;T;T;T;T
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.60	D;D;D;D;D;D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.7	M;.;M;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.6	D;D;D;D;D;D
REVEL	Uncertain	0.49
Sift	Uncertain	0.024	D;D;D;D;T;T
Sift4G	Benign	0.12	T;T;T;T;T;T
Polyphen		0.98	D;D;D;P;.;.
Vest4		0.37
MutPred		0.55		Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);.;.;
MVP		0.93
MPC		0.96
ClinPred		0.87	D
GERP RS		5.7
Varity_R		0.43
gMVP		0.84

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: chr4-155531333;