rs3222751

Positions:

• chr19-8085256-C-CACACACACACACACACACACACACACA
• chr19-8085256-C-CACACACACACACACACACACACACACACA
• chr19-8085256-C-CACACACACACACACACACACACACACACACA
• chr19-8085256-C-CACACACACACACACACACACACACACACACACA
• chr19-8085256-C-CACACACACACACACACACACACACACACACACACA
• chr19-8085256-C-CACACACACACACACACACACACACACACACACACACA
• chr19-8085256-C-CACACACACACACACACACACACACACACACACACACACA
• chr19-8085256-C-CACACACACACACACACACACACACACACACACACACACACA
• chr19-8085256-C-CACACACACACACACACACACACACACACACACACACACACACA
• chr19-8085256-C-CACACACACACACACACACACACACACACACACACACACACACACA
• chr19-8085256-C-CACACACAG
• chr19-8085256-C-CACAG

Variant summary

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

The NM_032447.5(FBN3):​c.7087+106_7087+107insTGTGTGTGTGTGTGTGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBN3	NM_032447.5	c.7087+106_7087+107insTGTGTGTGTGTGTGTGTGTGTGTGTGT		intron_variant		ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.7087+106_7087+107insTGTGTGTGTGTGTGTGTGTGTGTGTGT		intron_variant		1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.7087+106_7087+107insTGTGTGTGTGTGTGTGTGTGTGTGTGT		intron_variant		1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.7087+106_7087+107insTGTGTGTGTGTGTGTGTGTGTGTGTGT		intron_variant		1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.7213+106_7213+107insTGTGTGTGTGTGTGTGTGTGTGTGTGT		intron_variant				ENSP00000498507.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3222751; hg19: chr19-8150140;