Genetic Variant POU3F3:p.Gly42dup (chr2-104855630-C-CGGG) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

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

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.65

Publications

0 publications found

Variant links:

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]

POU3F3 links:

ENSG00000269707 (HGNC:):

ENSG00000269707 links:

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]

PANTR1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2591665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 48 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POU3F3	NM_006236.3	MANE Select	c.123_125dupGGG	p.Gly42dup	disruptive_inframe_insertion	Exon 1 of 1	NP_006227.1	P20264
POU3F3	NM_001433704.1		c.123_125dupGGG	p.Gly42dup	disruptive_inframe_insertion	Exon 2 of 2	NP_001420633.1	P20264
POU3F3	NR_197431.1		n.294+2064_294+2066dupGGG		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POU3F3	ENST00000361360.4	TSL:6 MANE Select	c.123_125dupGGG	p.Gly42dup	disruptive_inframe_insertion	Exon 1 of 1	ENSP00000355001.2	P20264
POU3F3	ENST00000674056.1		c.123_125dupGGG	p.Gly42dup	disruptive_inframe_insertion	Exon 4 of 4	ENSP00000501036.1	P20264
ENSG00000269707	ENST00000598623.1	TSL:5	n.345+1801_345+1803dupGGG		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000896

AC:

AN:

53596

Hom.:

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00160

AC XY:

216

AN XY:

135220

show subpopulations

African (AFR)

AF:

0.000174

AC:

AN:

5750

American (AMR)

AF:

0.00

AC:

AN:

430

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1804

East Asian (EAS)

AF:

0.00

AC:

AN:

1462

South Asian (SAS)

AF:

0.00130

AC:

AN:

6156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

154

Middle Eastern (MID)

AF:

0.00361

AC:

AN:

554

European-Non Finnish (NFE)

AF:

0.00148

AC:

394

AN:

265680

Other (OTH)

AF:

0.00199

AC:

AN:

9538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000896

AC:

AN:

53596

Hom.:

Cov.:

AF XY:

0.000923

AC XY:

AN XY:

25990

show subpopulations

African (AFR)

AF:

0.000136

AC:

AN:

14750

American (AMR)

AF:

0.000225

AC:

AN:

4444

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1480

East Asian (EAS)

AF:

0.00

AC:

AN:

1928

South Asian (SAS)

AF:

0.00124

AC:

AN:

1610

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1718

Middle Eastern (MID)

AF:

0.0122

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00147

AC:

AN:

26498

Other (OTH)

AF:

0.00421

AC:

AN:

712

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.6

Mutation Taster

=85/15

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over