chr3-70977859-G-A

Variant names:

• chr3-70977859-G-A
• rs794727155
• NM_001349338.3:c.1317C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_001349338.3(FOXP1):​c.1317C>T​(p.Tyr439Tyr) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FOXP1 NM_001349338.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.53
• 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina, ClinGen
• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000285708 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.236).
• BP6: Variant 3-70977859-G-A is Benign according to our data. Variant chr3-70977859-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3714359.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1317C>T	p.Tyr439Tyr	synonymous	Exon 15 of 21	NP_001336267.1	Q548T7
	FOXP1	NM_001244810.2		c.1317C>T	p.Tyr439Tyr	synonymous	Exon 15 of 21	NP_001231739.1	Q9H334-8
	FOXP1	NM_001244814.3		c.1317C>T	p.Tyr439Tyr	synonymous	Exon 11 of 17	NP_001231743.1	Q9H334-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXP1	ENST00000649528.3	MANE Select	c.1317C>T	p.Tyr439Tyr	synonymous	Exon 15 of 21	ENSP00000497369.1	Q9H334-1
	FOXP1	ENST00000318789.11	TSL:1	c.1317C>T	p.Tyr439Tyr	synonymous	Exon 15 of 21	ENSP00000318902.5	Q9H334-1
	ENSG00000285708	ENST00000647725.1		c.1317C>T	p.Tyr439Tyr	synonymous	Exon 20 of 26	ENSP00000497585.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	11
DANN	Benign	0.55
PhyloP100		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs794727155; hg19: chr3-71027010;