Variant 6-41565807-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001012426.2(FOXP4):c.47G>A(p.Gly16Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000024 in 1,461,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

FOXP4
NM_001012426.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.43

Variant links:

Genes affected

FOXP4 (HGNC:20842): (forkhead box P4) This gene belongs to subfamily P of the forkhead box (FOX) transcription factor family. Forkhead box transcription factors play important roles in the regulation of tissue- and cell type-specific gene transcription during both development and adulthood. Many members of the forkhead box gene family, including members of subfamily P, have roles in mammalian oncogenesis. This gene may play a role in the development of tumors of the kidney and larynx. Alternative splicing of this gene produces multiple transcript variants, some encoding different isoforms. [provided by RefSeq, Jul 2008]

FOXP4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08920607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP4	NM_001012426.2 link	c.47G>A	p.Gly16Asp	missense_variant	2/17	ENST00000307972.10	NP_001012426.1	Q8IVH2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXP4	ENST00000307972.10 link	c.47G>A	p.Gly16Asp	missense_variant	2/17	1	NM_001012426.2	ENSP00000309823.4		Q8IVH2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000480

AC:

AN:

250256

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

135460

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000654

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000240

AC:

AN:

1461340

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

726936

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000882

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 23, 2021

The c.47G>A (p.G16D) alteration is located in exon 2 (coding exon 1) of the FOXP4 gene. This alteration results from a G to A substitution at nucleotide position 47, causing the glycine (G) at amino acid position 16 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Benign

0.93

DEOGEN2

Benign

0.11

T;.;.;.;T

Eigen

Benign

-0.096

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.86

D;D;D;D;.

M_CAP

Benign

0.039

MetaRNN

Benign

0.089

T;T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.1

L;L;.;L;L

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.50

N;N;N;N;N

REVEL

Uncertain

0.31

Sift

Benign

0.17

T;T;T;T;T

Sift4G

Benign

0.80

T;T;T;T;T

Polyphen

0.27

B;.;.;.;B

Vest4

0.32

MutPred

0.12

Loss of glycosylation at S15 (P = 0.0448);Loss of glycosylation at S15 (P = 0.0448);Loss of glycosylation at S15 (P = 0.0448);Loss of glycosylation at S15 (P = 0.0448);Loss of glycosylation at S15 (P = 0.0448);

MVP

0.59

MPC

0.12

ClinPred

0.072

GERP RS

5.3

Varity_R

0.056

gMVP

0.20

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