2-104855630-C-CGGG

Position:

• chr2-104855630-C-CGGG

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_006236.3(POU3F3):​c.123_125dupGGG​(p.Gly42dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 345,124 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00090 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0015 (2 hom.)
• Consequence: POU3F3 NM_006236.3 disruptive_inframe_insertion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 Benign. Variant got -12 ACMG points.

• BP6: Variant 2-104855630-C-CGGG is Benign according to our data. Variant chr2-104855630-C-CGGG is described in ClinVar as [Benign]. Clinvar id is 2591665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 48 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU3F3	NM_006236.3	c.123_125dupGGG	p.Gly42dup	disruptive_inframe_insertion	1/1	ENST00000361360.4	NP_006227.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU3F3	ENST00000361360.4	c.123_125dupGGG	p.Gly42dup	disruptive_inframe_insertion	1/1	6	NM_006236.3	ENSP00000355001.2

Frequencies

GnomAD3 genomes AF: 0.000896 AC: 48 AN: 53596 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.000136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000225

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0122

Gnomad NFE AF: 0.00147

Gnomad OTH AF: 0.00421

GnomAD4 exome AF: 0.00145 AC: 424 AN: 291528 Hom.: 2 Cov.: 25 AF XY: 0.00160 AC XY: 216 AN XY: 135220

Gnomad4 AFR exome AF: 0.000174

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00130

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00148

Gnomad4 OTH exome AF: 0.00199

GnomAD4 genome AF: 0.000896 AC: 48 AN: 53596 Hom.: 0 Cov.: 26 AF XY: 0.000923 AC XY: 24 AN XY: 25990

Gnomad4 AFR AF: 0.000136

Gnomad4 AMR AF: 0.000225

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00147

Gnomad4 OTH AF: 0.00421

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2023

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

POU3F3: BS1, BS2 -

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: rs1303053833; hg19: chr2-105472088;