1-47417035-C-T

Variant names:

• chr1-47417035-C-T
• rs80358194
• NM_012186.3:c.720C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_012186.3(FOXE3):​c.720C>T​(p.Cys240Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000854 in 1,171,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: FOXE3 NM_012186.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.205
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=0.205 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXE3	NM_012186.3	c.720C>T	p.Cys240Cys	synonymous_variant	Exon 1 of 1	ENST00000335071.4	NP_036318.1
LINC01389	NR_126355.1	n.29-7134G>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXE3	ENST00000335071.4	c.720C>T	p.Cys240Cys	synonymous_variant	Exon 1 of 1	6	NM_012186.3	ENSP00000334472.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.54e-7 AC: 1 AN: 1171314 Hom.: 0 Cov.: 34 AF XY: 0.00000174 AC XY: 1 AN XY: 574358

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22620

American (AMR) AF: 0.00 AC: 0 AN: 13554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17156

East Asian (EAS) AF: 0.0000439 AC: 1 AN: 22796

South Asian (SAS) AF: 0.00 AC: 0 AN: 51232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3198

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 967854

Other (OTH) AF: 0.00 AC: 0 AN: 46002

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism

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: rs80358194; hg19: chr1-47882707;