3-70955832-G-GCGCACACACACACA

Variant names:

• chr3-70955832-G-GCGCACACACACACA
• rs1553648184
• NM_001349338.3:c.*3414_*3415insTGTGTGTGTGTGCG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001349338.3(FOXP1):​c.*3414_*3415insTGTGTGTGTGTGCG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000269 in 74,370 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: FOXP1 NM_001349338.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.373
• 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.*3414_*3415insTGTGTGTGTGTGCG		3_prime_UTR	Exon 21 of 21	NP_001336267.1	Q548T7
	FOXP1	NM_001244810.2		c.*3414_*3415insTGTGTGTGTGTGCG		3_prime_UTR	Exon 21 of 21	NP_001231739.1	Q9H334-8
	FOXP1	NM_001244814.3		c.*3414_*3415insTGTGTGTGTGTGCG		3_prime_UTR	Exon 17 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.*3414_*3415insTGTGTGTGTGTGCG		3_prime_UTR	Exon 21 of 21	ENSP00000497369.1	Q9H334-1
	FOXP1	ENST00000318789.11	TSL:1	c.*3414_*3415insTGTGTGTGTGTGCG		3_prime_UTR	Exon 21 of 21	ENSP00000318902.5	Q9H334-1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.0000269 AC: 2 AN: 74370 Hom.: 0 Cov.: 0 AF XY: 0.0000293 AC XY: 1 AN XY: 34160

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 3810

American (AMR) AF: 0.00 AC: 0 AN: 2292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4646

East Asian (EAS) AF: 0.000181 AC: 2 AN: 11050

South Asian (SAS) AF: 0.00 AC: 0 AN: 712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 446

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 44954

Other (OTH) AF: 0.00 AC: 0 AN: 6144

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1553648184; hg19: chr3-71004983;