3-70955570-GTTTT-GTTTTTTT

Variant names:

• chr3-70955570-G-GTTT
• rs35502550
• NM_001349338.3:c.*3674_*3676dupAAA

Variant summary

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

The NM_001349338.3(FOXP1):​c.*3674_*3676dupAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000598 in 217,348 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000069 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: FOXP1 NM_001349338.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.620
• Publications: 1 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

ACMG classification

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.*3674_*3676dupAAA		3_prime_UTR_variant	Exon 21 of 21	ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3	c.*3674_*3676dupAAA		3_prime_UTR_variant	Exon 21 of 21		NM_001349338.3	ENSP00000497369.1
FOXP1	ENST00000318789.11	c.*3674_*3676dupAAA		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000318902.5

Frequencies

GnomAD3 genomes AF: 0.00000691 AC: 1 AN: 144734 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000165 AC: 12 AN: 72614 Hom.: 0 Cov.: 0 AF XY: 0.000119 AC XY: 4 AN XY: 33498

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

African (AFR) AF: 0.000843 AC: 3 AN: 3560

American (AMR) AF: 0.000454 AC: 1 AN: 2204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4582

East Asian (EAS) AF: 0.000655 AC: 7 AN: 10688

South Asian (SAS) AF: 0.00 AC: 0 AN: 642

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 464

European-Non Finnish (NFE) AF: 0.0000226 AC: 1 AN: 44270

Other (OTH) AF: 0.00 AC: 0 AN: 6024

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000691 AC: 1 AN: 144734 Hom.: 0 Cov.: 30 AF XY: 0.0000142 AC XY: 1 AN XY: 70344

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

African (AFR) AF: 0.0000250 AC: 1 AN: 39964

American (AMR) AF: 0.00 AC: 0 AN: 14402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3352

East Asian (EAS) AF: 0.00 AC: 0 AN: 5044

South Asian (SAS) AF: 0.00 AC: 0 AN: 4582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 296

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65272

Other (OTH) AF: 0.00 AC: 0 AN: 1978

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.62

Splicing

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

Other links and lift over

dbSNP: rs35502550; hg19: chr3-71004721;