NM_032447.5:c.8224G>T

Variant names:

• chr19-8066125-C-A
• NM_032447.5:c.8224G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032447.5(FBN3):​c.8224G>T​(p.Val2742Phe) 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 benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FBN3 NM_032447.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159

Genes affected

FBN3 (HGNC:18794): (fibrillin 3) This gene encodes a memebr of the fibrillin protein family. Fibrillins are extracellular matrix molecules that assemble into microfibrils in many connective tissues. This gene is most highly expressed in fetal tissues and its protein product is localized to extracellular microfibrils of developing skeletal elements, skin, lung, kidney, and skeletal muscle. This gene is potentially involved in Weill-Marchesani syndrome. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093262374).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN3	NM_032447.5	c.8224G>T	p.Val2742Phe	missense_variant	Exon 64 of 64	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.8224G>T	p.Val2742Phe	missense_variant	Exon 64 of 64	1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.8224G>T	p.Val2742Phe	missense_variant	Exon 63 of 63	1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.8224G>T	p.Val2742Phe	missense_variant	Exon 64 of 64	1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.8350G>T	p.Val2784Phe	missense_variant	Exon 64 of 64			ENSP00000498507.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	10
DANN	Benign	0.91
DEOGEN2	Benign	0.058	T;T;T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.87	.;.;D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.093	T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	0.0	N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.2	.;N;.
REVEL	Benign	0.22
Sift	Benign	0.042	.;D;.
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.33	B;B;B
Vest4		0.078
MutPred		0.44		Loss of MoRF binding (P = 0.0916);Loss of MoRF binding (P = 0.0916);Loss of MoRF binding (P = 0.0916);
MVP		0.71
MPC		0.32
ClinPred		0.20	T
GERP RS		2.2
Varity_R		0.068
gMVP		0.60

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: chr19-8131009;