rs79691946

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001453.3(FOXC1):c.889C>T(p.Pro297Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0058 in 1,419,488 control chromosomes in the GnomAD database, including 351 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 182 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 169 hom. )

Consequence

FOXC1
NM_001453.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:2B:4

Conservation

PhyloP100: 1.69

Variant links:

Genes affected

FOXC1 (HGNC:3800): (forkhead box C1) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct DNA-binding forkhead domain. The specific function of this gene has not yet been determined; however, it has been shown to play a role in the regulation of embryonic and ocular development. Mutations in this gene cause various glaucoma phenotypes including primary congenital glaucoma, autosomal dominant iridogoniodysgenesis anomaly, and Axenfeld-Rieger anomaly. [provided by RefSeq, Jul 2008]

FOXC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017443299).

BP6

Variant 6-1611334-C-T is Benign according to our data. Variant chr6-1611334-C-T is described in ClinVar as [Benign]. Clinvar id is 30156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-1611334-C-T is described in Lovd as [Likely_pathogenic].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXC1	NM_001453.3 link	c.889C>T	p.Pro297Ser	missense_variant	Exon 1 of 1	ENST00000645831.2	NP_001444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXC1	ENST00000645831.2 link	c.889C>T	p.Pro297Ser	missense_variant	Exon 1 of 1		NM_001453.3	ENSP00000493906.1		Q12948

Frequencies

GnomAD3 genomes

AF:

0.0286

AC:

4293

AN:

150208

Hom.:

179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0127

Gnomad ASJ

AF:

0.000582

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000847

Gnomad OTH

AF:

0.0257

GnomAD3 exomes

AF:

0.00284

AC:

213

AN:

75104

Hom.:

AF XY:

0.00217

AC XY:

AN XY:

43388

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.00515

Gnomad ASJ exome

AF:

0.000460

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000183

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000691

Gnomad OTH exome

AF:

0.00461

GnomAD4 exome

AF:

0.00310

AC:

3930

AN:

1269172

Hom.:

169

Cov.:

AF XY:

0.00269

AC XY:

1685

AN XY:

625620

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.00611

Gnomad4 ASJ exome

AF:

0.000329

Gnomad4 EAS exome

AF:

0.0000389

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000532

Gnomad4 OTH exome

AF:

0.00700

GnomAD4 genome

AF:

0.0286

AC:

4301

AN:

150316

Hom.:

182

Cov.:

AF XY:

0.0271

AC XY:

1986

AN XY:

73418

show subpopulations

Gnomad4 AFR

AF:

0.0966

Gnomad4 AMR

AF:

0.0126

Gnomad4 ASJ

AF:

0.000582

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000847

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.0209

Hom.:

Bravo

AF:

0.0320

ExAC

AF:

0.00247

AC:

189

ClinVar

Significance: Benign

Submissions summary: Pathogenic:2Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Pathogenic:1Benign:1

Human Genetics School of Medicine of Albacete, Castilla-La Mancha University

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27884173, 17197537, 25093829, 21423868, 19626132, 19793056) -

not specified

Benign:2

Mar 23, 2020

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 21, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Anterior segment dysgenesis 3

Pathogenic:1

Sep 01, 2009

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Axenfeld-Rieger syndrome type 3

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.37

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.34

.;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-0.65

MutationAssessor

Benign

0.69

N;N

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.7

N;.

REVEL

Benign

0.19

Sift

Benign

0.17

T;.

Sift4G

Benign

0.65

T;.

Polyphen

0.26

B;B

Vest4

0.14

MVP

0.81

ClinPred

0.0048

GERP RS

-0.40

Varity_R

0.044

gMVP

0.32

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over