rs387906793

Variant names:

• chr1-47417274-G-C
• rs387906793
• NM_012186.3:c.959G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-47417274-G-C
• chr1-47417274-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_012186.3(FOXE3):​c.959G>C​(p.Ter320Serext*?) variant causes a stop lost 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. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXE3 NM_012186.3 stop_lost
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.16
• Publications: 2 publications found

Genes affected

FOXE3 (HGNC:3808): (forkhead box E3) This intronless gene belongs to the forkhead family of transcription factors, which is characterized by a distinct forkhead domain. The protein encoded functions as a lens-specific transcription factor and plays an important role in vertebrate lens formation. Mutations in this gene are associated with anterior segment mesenchymal dysgenesis and congenital primary aphakia. [provided by RefSeq, Dec 2009]

LINC01389 (HGNC:50661): (long intergenic non-protein coding RNA 1389)

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_012186.3 Downstream stopcodon found after 329 codons.
• PP5: Variant 1-47417274-G-C is Pathogenic according to our data. Variant chr1-47417274-G-C is described in ClinVar as Pathogenic. ClinVar VariationId is 1077109.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXE3	NM_012186.3	c.959G>C	p.Ter320Serext*?	stop_lost	Exon 1 of 1	ENST00000335071.4	NP_036318.1
LINC01389	NR_126355.1	n.29-7373C>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXE3	ENST00000335071.4	c.959G>C	p.Ter320Serext*?	stop_lost	Exon 1 of 1	6	NM_012186.3	ENSP00000334472.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1201798 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 585616

African (AFR) AF: 0.00 AC: 0 AN: 24356

American (AMR) AF: 0.00 AC: 0 AN: 14748

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17736

East Asian (EAS) AF: 0.00 AC: 0 AN: 27024

South Asian (SAS) AF: 0.00 AC: 0 AN: 51570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3356

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 985522

Other (OTH) AF: 0.00 AC: 0 AN: 48624

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Cataract 34 multiple types Pathogenic:1

May 01, 2021

Human Developmental Genetics Laboratory, Medical College of Wisconsin

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.84
Eigen	Pathogenic	0.74
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		2.2
Vest4		0.047
GERP RS		3.8
Mutation Taster		=38/62	disease causing

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

Other links and lift over

dbSNP: rs387906793; hg19: chr1-47882946;