3-71198338-G-T

Variant names:

• chr3-71198338-G-T
• rs532329866
• NM_001349338.3:c.44C>A

Variant summary

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

The NM_001349338.3(FOXP1):​c.44C>A​(p.Ala15Asp) variant causes a missense change. 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. A15V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FOXP1 NM_001349338.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.00
• Publications: 0 publications found

Genes affected

FOXP1 (HGNC:3823): (forkhead box P1) 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. Forkhead box P1 protein contains both DNA-binding- and protein-protein binding-domains. This gene may act as a tumor suppressor as it is lost in several tumor types and maps to a chromosomal region (3p14.1) reported to contain a tumor suppressor gene(s). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

FOXP1 Gene-Disease associations (from GenCC):

• intellectual disability-severe speech delay-mild dysmorphism syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000285708 (HGNC:):

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=0.35714135).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349338.3. 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
	FOXP1	NM_001349338.3	MANE Select	c.44C>A	p.Ala15Asp	missense	Exon 6 of 21	NP_001336267.1
	FOXP1	NM_001244810.2		c.44C>A	p.Ala15Asp	missense	Exon 6 of 21	NP_001231739.1
	FOXP1	NM_001244814.3		c.44C>A	p.Ala15Asp	missense	Exon 2 of 17	NP_001231743.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	ENST00000649528.3	MANE Select	c.44C>A	p.Ala15Asp	missense	Exon 6 of 21	ENSP00000497369.1
	FOXP1	ENST00000318789.11	TSL:1	c.44C>A	p.Ala15Asp	missense	Exon 6 of 21	ENSP00000318902.5
	ENSG00000285708	ENST00000647725.1		c.44C>A	p.Ala15Asp	missense	Exon 11 of 26	ENSP00000497585.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.070	D
MetaRNN	Benign	0.36	T
MetaSVM	Uncertain	0.63	D
MutationAssessor	Benign	2.0	M
PhyloP100		7.0
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.47
Sift	Uncertain	0.029	D
Sift4G	Benign	0.094	T
Polyphen		0.18	B
Vest4		0.54
MutPred		0.093		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.55
ClinPred		0.82	D
GERP RS		5.6
PromoterAI		-0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.46
Mutation Taster		=17/83	disease causing

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: rs532329866; hg19: chr3-71247489;