1-47417244-G-T

Variant names:

• chr1-47417244-G-T
• rs571095192
• NM_012186.3:c.929G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_012186.3(FOXE3):​c.929G>T​(p.Gly310Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G310D) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXE3 NM_012186.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21642566).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012186.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXE3	NM_012186.3	MANE Select	c.929G>T	p.Gly310Val	missense	Exon 1 of 1	NP_036318.1	Q13461
	LINC01389	NR_126355.1		n.29-7343C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXE3	ENST00000335071.4	TSL:6 MANE Select	c.929G>T	p.Gly310Val	missense	Exon 1 of 1	ENSP00000334472.2	Q13461
	LINC01389	ENST00000828806.1		n.79C>A		non_coding_transcript_exon	Exon 1 of 3
	LINC01389	ENST00000828807.1		n.79C>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151904 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

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: 1203312 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 586506

African (AFR) AF: 0.00 AC: 0 AN: 24000

American (AMR) AF: 0.00 AC: 0 AN: 11650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17228

East Asian (EAS) AF: 0.00 AC: 0 AN: 27090

South Asian (SAS) AF: 0.00 AC: 0 AN: 50208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3378

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 991578

Other (OTH) AF: 0.00 AC: 0 AN: 49056

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151904 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74202

African (AFR) AF: 0.0000242 AC: 1 AN: 41380

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67906

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.61	T
M_CAP	Pathogenic	0.92	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.25
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.22
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.015	D
Polyphen		0.51	P
Vest4		0.19
MutPred		0.32		Loss of disorder (P = 0.0101)
MVP		0.54
ClinPred		0.16	T
GERP RS		1.6
Varity_R		0.10
gMVP		0.23
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs571095192; hg19: chr1-47882916;