19-8085256-C-CACAG

Variant names:

• chr19-8085256-C-CACAG
• rs3222751
• NM_032447.5:c.7087+106_7087+107insCTGT

Variant summary

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

The NM_032447.5(FBN3):​c.7087+106_7087+107insCTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 148,848 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: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FBN3 NM_032447.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.393
• Publications: 1 publications found

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

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
FBN3	NM_032447.5	c.7087+106_7087+107insCTGT		intron_variant	Intron 56 of 63	ENST00000600128.6	NP_115823.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN3	ENST00000600128.6	c.7087+106_7087+107insCTGT		intron_variant	Intron 56 of 63	1	NM_032447.5	ENSP00000470498.1
FBN3	ENST00000270509.6	c.7087+106_7087+107insCTGT		intron_variant	Intron 55 of 62	1		ENSP00000270509.2
FBN3	ENST00000601739.5	c.7087+106_7087+107insCTGT		intron_variant	Intron 56 of 63	1		ENSP00000472324.1
FBN3	ENST00000651877.1	c.7213+106_7213+107insCTGT		intron_variant	Intron 56 of 63			ENSP00000498507.1

Frequencies

GnomAD3 genomes AF: 0.0000134 AC: 2 AN: 148848 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000496

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 719478 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 375682

African (AFR) AF: 0.00 AC: 0 AN: 16476

American (AMR) AF: 0.00 AC: 0 AN: 20404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18916

East Asian (EAS) AF: 0.00 AC: 0 AN: 31534

South Asian (SAS) AF: 0.00 AC: 0 AN: 59076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2688

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 497582

Other (OTH) AF: 0.00 AC: 0 AN: 35450

GnomAD4 genome AF: 0.0000134 AC: 2 AN: 148848 Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 1 AN XY: 72576

African (AFR) AF: 0.0000496 AC: 2 AN: 40324

American (AMR) AF: 0.00 AC: 0 AN: 14856

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3430

East Asian (EAS) AF: 0.00 AC: 0 AN: 4996

South Asian (SAS) AF: 0.00 AC: 0 AN: 4680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66970

Other (OTH) AF: 0.00 AC: 0 AN: 2048

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.39

Splicing

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

Other links and lift over

dbSNP: rs3222751; hg19: chr19-8150140;