NM_006236.3:c.131_148dupCAGGGGGCGGGGGCGGCG

Variant names:

• chr2-104855627-C-CGGCGGGGGCGGCGCAGGG
• rs1296804946
• NM_006236.3:c.131_148dupCAGGGGGCGGGGGCGGCG

Variant summary

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

The NM_006236.3(POU3F3):​c.131_148dupCAGGGGGCGGGGGCGGCG​(p.Ala44_Gly49dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000175 in 570,352 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: 0.0000018 (0 hom.)
• Consequence: POU3F3 NM_006236.3 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 0 publications found

Genes affected

POU3F3 (HGNC:9216): (POU class 3 homeobox 3) This gene encodes a POU-domain containing protein that functions as a transcription factor. The encoded protein recognizes an octamer sequence in the DNA of target genes. This protein may play a role in development of the nervous system. [provided by RefSeq, Apr 2015]

ENSG00000269707 (HGNC:):

PANTR1 (HGNC:49513): (POU3F3 adjacent non-coding transcript 1) Predicted to act upstream of or within regulation of gene expression. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006236.3. 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
	POU3F3	NM_006236.3	MANE Select	c.131_148dupCAGGGGGCGGGGGCGGCG	p.Ala44_Gly49dup	disruptive_inframe_insertion	Exon 1 of 1	NP_006227.1	P20264
	POU3F3	NM_001433704.1		c.131_148dupCAGGGGGCGGGGGCGGCG	p.Ala44_Gly49dup	disruptive_inframe_insertion	Exon 2 of 2	NP_001420633.1	P20264
	POU3F3	NR_197431.1		n.294+2072_294+2089dupCAGGGGGCGGGGGCGGCG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU3F3	ENST00000361360.4	TSL:6 MANE Select	c.131_148dupCAGGGGGCGGGGGCGGCG	p.Ala44_Gly49dup	disruptive_inframe_insertion	Exon 1 of 1	ENSP00000355001.2	P20264
	POU3F3	ENST00000674056.1		c.131_148dupCAGGGGGCGGGGGCGGCG	p.Ala44_Gly49dup	disruptive_inframe_insertion	Exon 4 of 4	ENSP00000501036.1	P20264
	ENSG00000269707	ENST00000598623.1	TSL:5	n.345+1809_345+1826dupCAGGGGGCGGGGGCGGCG		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome AF: 0.00000175 AC: 1 AN: 570352 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 264758

African (AFR) AF: 0.00 AC: 0 AN: 10976

American (AMR) AF: 0.00134 AC: 1 AN: 746

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3522

East Asian (EAS) AF: 0.00 AC: 0 AN: 2666

South Asian (SAS) AF: 0.00 AC: 0 AN: 11858

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1104

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 520450

Other (OTH) AF: 0.00 AC: 0 AN: 18786

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs1296804946; hg19: chr2-105472085;