chr2-104855585-CGCGGCAGGGGCTGGCG-C

Variant names:

• chr2-104855585-CGCGGCAGGGGCTGGCG-C
• NM_006236.3:c.81_96delAGGGGCTGGCGGCGGC

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PP5_Moderate

The NM_006236.3(POU3F3):​c.81_96delAGGGGCTGGCGGCGGC​(p.Ala29ValfsTer25) variant causes a frameshift change. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 15)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POU3F3 NM_006236.3 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.69
• 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: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 51 pathogenic variants in the truncated region.
• PP5: Variant 2-104855585-CGCGGCAGGGGCTGGCG-C is Pathogenic according to our data. Variant chr2-104855585-CGCGGCAGGGGCTGGCG-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 3775399.Status of the report is criteria_provided_single_submitter, 1 stars.

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.81_96delAGGGGCTGGCGGCGGC	p.Ala29ValfsTer25	frameshift	Exon 1 of 1	NP_006227.1	P20264
	POU3F3	NM_001433704.1		c.81_96delAGGGGCTGGCGGCGGC	p.Ala29ValfsTer25	frameshift	Exon 2 of 2	NP_001420633.1	P20264
	POU3F3	NR_197431.1		n.294+2022_294+2037delAGGGGCTGGCGGCGGC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU3F3	ENST00000361360.4	TSL:6 MANE Select	c.81_96delAGGGGCTGGCGGCGGC	p.Ala29ValfsTer25	frameshift	Exon 1 of 1	ENSP00000355001.2	P20264
	POU3F3	ENST00000674056.1		c.81_96delAGGGGCTGGCGGCGGC	p.Ala29ValfsTer25	frameshift	Exon 4 of 4	ENSP00000501036.1	P20264
	ENSG00000269707	ENST00000598623.1	TSL:5	n.345+1759_345+1774delAGGGGCTGGCGGCGGC		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 15

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 863026 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 405082

African (AFR) AF: 0.00 AC: 0 AN: 16128

American (AMR) AF: 0.00 AC: 0 AN: 2256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6892

East Asian (EAS) AF: 0.00 AC: 0 AN: 4038

South Asian (SAS) AF: 0.00 AC: 0 AN: 22730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 778816

Other (OTH) AF: 0.00 AC: 0 AN: 28362

GnomAD4 genome Cov.: 15

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Snijders blok-fisher syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.7

Splicing

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

Other links and lift over

hg19: chr2-105472043;