NM_023067.4:c.*925dupT

Variant names:

• chr3-138944666-C-CA
• rs139209636
• NM_023067.4:c.*925dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_023067.4(FOXL2):​c.*925dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0552 in 233,188 control chromosomes in the GnomAD database, including 709 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.064 (591 hom., cov: 32)
  • Exomes 𝑓: 0.038 (118 hom.)
• Consequence: FOXL2 NM_023067.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.52
• Publications: 0 publications found

Genes affected

FOXL2 (HGNC:1092): (forkhead box L2) This gene encodes a forkhead transcription factor. The protein contains a fork-head DNA-binding domain and may play a role in ovarian development and function. Expansion of a polyalanine repeat region and other mutations in this gene are a cause of blepharophimosis syndrome and premature ovarian failure 3. [provided by RefSeq, Jul 2016]

FOXL2 Gene-Disease associations (from GenCC):

• blepharophimosis, ptosis, and epicanthus inversus syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• premature ovarian failure 3

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-138944666-C-CA is Benign according to our data. Variant chr3-138944666-C-CA is described in ClinVar as Benign. ClinVar VariationId is 1228805.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023067.4. 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
	FOXL2	NM_023067.4	MANE Select	c.*925dupT		3_prime_UTR	Exon 1 of 1	NP_075555.1	Q53ZD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXL2	ENST00000648323.1	MANE Select	c.*925dupT		3_prime_UTR	Exon 1 of 1	ENSP00000497217.1	P58012

Frequencies

GnomAD3 genomes AF: 0.0640 AC: 9744 AN: 152190 Hom.: 584 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0308

Gnomad ASJ AF: 0.0302

Gnomad EAS AF: 0.0323

Gnomad SAS AF: 0.0835

Gnomad FIN AF: 0.0628

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0208

Gnomad OTH AF: 0.0540

GnomAD4 exome AF: 0.0382 AC: 3086 AN: 80880 Hom.: 118 Cov.: 0 AF XY: 0.0374 AC XY: 1391 AN XY: 37172

African (AFR) AF: 0.151 AC: 586 AN: 3886

American (AMR) AF: 0.0244 AC: 61 AN: 2498

Ashkenazi Jewish (ASJ) AF: 0.0281 AC: 144 AN: 5116

East Asian (EAS) AF: 0.0915 AC: 1042 AN: 11392

South Asian (SAS) AF: 0.0755 AC: 53 AN: 702

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 60

Middle Eastern (MID) AF: 0.0447 AC: 22 AN: 492

European-Non Finnish (NFE) AF: 0.0195 AC: 972 AN: 49966

Other (OTH) AF: 0.0304 AC: 206 AN: 6768

GnomAD4 genome AF: 0.0642 AC: 9781 AN: 152308 Hom.: 591 Cov.: 32 AF XY: 0.0651 AC XY: 4847 AN XY: 74474

African (AFR) AF: 0.154 AC: 6385 AN: 41546

American (AMR) AF: 0.0308 AC: 471 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0302 AC: 105 AN: 3472

East Asian (EAS) AF: 0.0324 AC: 168 AN: 5188

South Asian (SAS) AF: 0.0836 AC: 404 AN: 4832

European-Finnish (FIN) AF: 0.0628 AC: 666 AN: 10610

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0208 AC: 1413 AN: 68030

Other (OTH) AF: 0.0605 AC: 128 AN: 2114

Alfa AF: 0.0494 Hom.: 37

Bravo AF: 0.0618

Asia WGS AF: 0.0720 AC: 252 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs139209636; hg19: chr3-138663508;