16-86510583-C-A

Variant names:

• chr16-86510583-C-A
• rs1463030533
• NM_001451.3:c.14C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001451.3(FOXF1):​c.14C>A​(p.Pro5His) variant causes a missense 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. 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. P5T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXF1 NM_001451.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58
• Publications: 0 publications found

Genes affected

FOXF1 (HGNC:3809): (forkhead box F1) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in the regulation of pulmonary genes as well as embryonic development. [provided by RefSeq, Jul 2008]

FOXF1 Gene-Disease associations (from GenCC):

• alveolar capillary dysplasia with misalignment of pulmonary veins

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28719395).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001451.3. 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
	FOXF1	NM_001451.3	MANE Select	c.14C>A	p.Pro5His	missense	Exon 1 of 2	NP_001442.2	Q12946

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXF1	ENST00000262426.6	TSL:1 MANE Select	c.14C>A	p.Pro5His	missense	Exon 1 of 2	ENSP00000262426.4	Q12946

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 36074 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1225156 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 600084

African (AFR) AF: 0.00 AC: 0 AN: 23838

American (AMR) AF: 0.00 AC: 0 AN: 13580

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18328

East Asian (EAS) AF: 0.00 AC: 0 AN: 27464

South Asian (SAS) AF: 0.00 AC: 0 AN: 51250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3670

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1004390

Other (OTH) AF: 0.00 AC: 0 AN: 49976

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.46	T
M_CAP	Pathogenic	0.85	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	0.066	D
MutationAssessor	Benign	0.0	N
PhyloP100		2.6
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.010	D
Polyphen		0.085	B
Vest4		0.37
MutPred		0.19		Loss of glycosylation at P5 (P = 0.0194)
MVP		0.43
ClinPred		0.46	T
GERP RS		2.5
PromoterAI		-0.040	Neutral
Varity_R		0.39
gMVP		0.32
Mutation Taster		=83/17	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: rs1463030533; hg19: chr16-86544189;