rs749611196

Positions:

• chr3-71053750-C-G
• chr3-71053750-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001349338.3(FOXP1):​c.306G>C​(p.Met102Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FOXP1 NM_001349338.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.90

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.306G>C	p.Met102Ile	missense_variant	8/21	ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3	c.306G>C	p.Met102Ile	missense_variant	8/21		NM_001349338.3	ENSP00000497369	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.72	D;.;D;.;D;.;.;.;.;.;.;.;D;.;.;.;D;.;.;D;.;.;.;.;.;.;.;T;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	.;D;.;.;.;.;D;.;.;D;D;D;.;.;D;.;.;D;D;D;D;D;D;D;D;D;D;D;.
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.53	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.63	D
MutationAssessor	Uncertain	2.6	M;M;M;M;M;.;.;.;M;.;.;.;M;.;.;.;M;M;.;M;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.6	D;.;D;D;.;.;.;.;.;.;.;.;D;.;.;N;.;.;.;.;.;D;.;.;D;.;D;.;.
REVEL	Benign	0.29
Sift	Benign	0.071	T;.;T;T;.;.;.;.;.;.;.;.;T;.;.;T;.;.;.;.;.;T;.;.;T;.;D;.;.
Sift4G	Benign	0.14	T;T;T;T;.;.;.;T;.;.;.;.;T;.;.;T;.;.;.;.;.;T;.;.;.;.;T;.;.
Polyphen		0.53	P;.;P;.;P;.;.;.;.;.;.;.;P;.;.;.;P;.;.;P;.;.;.;.;.;.;.;.;.
Vest4		0.74
MutPred		0.18		Gain of catalytic residue at P104 (P = 0.0327);Gain of catalytic residue at P104 (P = 0.0327);Gain of catalytic residue at P104 (P = 0.0327);Gain of catalytic residue at P104 (P = 0.0327);Gain of catalytic residue at P104 (P = 0.0327);Gain of catalytic residue at P104 (P = 0.0327);.;.;Gain of catalytic residue at P104 (P = 0.0327);Gain of catalytic residue at P104 (P = 0.0327);.;.;Gain of catalytic residue at P104 (P = 0.0327);.;Gain of catalytic residue at P104 (P = 0.0327);.;Gain of catalytic residue at P104 (P = 0.0327);Gain of catalytic residue at P104 (P = 0.0327);.;Gain of catalytic residue at P104 (P = 0.0327);.;Gain of catalytic residue at P104 (P = 0.0327);.;Gain of catalytic residue at P104 (P = 0.0327);.;.;.;Gain of catalytic residue at P104 (P = 0.0327);Gain of catalytic residue at P104 (P = 0.0327);
MVP		0.79
MPC		0.78
ClinPred		0.94	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-71102901;