chr2-104855627-CGGCGGGGGCGGCGCAGGG-C

Position:

• chr2-104855627-CGGCGGGGGCGGCGCAGGG-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_006236.3(POU3F3):​c.131_148delCAGGGGGCGGGGGCGGCG​(p.Ala44_Gly49del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 570,308 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000081 (0 hom., cov: 6)
  • Exomes 𝑓: 0.000042 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POU3F3 NM_006236.3 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.65

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:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 2-104855627-CGGCGGGGGCGGCGCAGGG-C is Benign according to our data. Variant chr2-104855627-CGGCGGGGGCGGCGCAGGG-C is described in ClinVar as [Likely_benign]. Clinvar id is 2651216.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU3F3	NM_006236.3	c.131_148delCAGGGGGCGGGGGCGGCG	p.Ala44_Gly49del	disruptive_inframe_deletion	1/1	ENST00000361360.4	NP_006227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU3F3	ENST00000361360.4	c.131_148delCAGGGGGCGGGGGCGGCG	p.Ala44_Gly49del	disruptive_inframe_deletion	1/1	6	NM_006236.3	ENSP00000355001.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 6 AN: 73708 Hom.: 0 Cov.: 6 FAILED QC

Gnomad AFR AF: 0.000151

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: 0.000396

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000273

Gnomad OTH AF: 0.00105

GnomAD4 exome AF: 0.0000421 AC: 24 AN: 570308 Hom.: 0 AF XY: 0.0000378 AC XY: 10 AN XY: 264740

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000375

Gnomad4 SAS exome AF: 0.000169

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000404

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000814 AC: 6 AN: 73708 Hom.: 0 Cov.: 6 AF XY: 0.0000848 AC XY: 3 AN XY: 35392

Gnomad4 AFR AF: 0.000151

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000396

Gnomad4 NFE AF: 0.0000273

Gnomad4 OTH AF: 0.00105

Alfa AF: 0.0000712 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

POU3F3: BP3 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1296804946; hg19: chr2-105472085;