Genetic Variant POU3F3:p.Gly30Gly (chr2-104855600-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_006236.3(POU3F3):c.90C>T(p.Gly30Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000211 in 924,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 21)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

POU3F3
NM_006236.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.557

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 2-104855600-C-T is Benign according to our data. Variant chr2-104855600-C-T is described in ClinVar as Benign. ClinVar VariationId is 2651214.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.557 with no splicing effect.

BS2

High AC in GnomAd4 at 54 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.90C>T	p.Gly30Gly	synonymous	Exon 1 of 1	NP_006227.1	P20264
POU3F3	NM_001433704.1		c.90C>T	p.Gly30Gly	synonymous	Exon 2 of 2	NP_001420633.1	P20264
POU3F3	NR_197431.1		n.294+2031C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POU3F3	ENST00000361360.4	TSL:6 MANE Select	c.90C>T	p.Gly30Gly	synonymous	Exon 1 of 1	ENSP00000355001.2	P20264
POU3F3	ENST00000674056.1		c.90C>T	p.Gly30Gly	synonymous	Exon 4 of 4	ENSP00000501036.1	P20264
ENSG00000269707	ENST00000598623.1	TSL:5	n.345+1768C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000568

AC:

AN:

93368

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000830

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00694

Gnomad NFE

AF:

0.0000858

Gnomad OTH

AF:

0.000795

GnomAD2 exomes

AF:

0.00

AC:

AN:

3002

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000170

AC:

141

AN:

830958

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

385502

show subpopulations

African (AFR)

AF:

0.00147

AC:

AN:

15678

American (AMR)

AF:

0.00

AC:

AN:

1144

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5456

East Asian (EAS)

AF:

0.00

AC:

AN:

3698

South Asian (SAS)

AF:

0.00

AC:

AN:

18140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

696

Middle Eastern (MID)

AF:

0.00123

AC:

AN:

1632

European-Non Finnish (NFE)

AF:

0.000145

AC:

110

AN:

757272

Other (OTH)

AF:

0.000220

AC:

AN:

27242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000578

AC:

AN:

93400

Hom.:

Cov.:

AF XY:

0.000764

AC XY:

AN XY:

44506

show subpopulations

African (AFR)

AF:

0.00163

AC:

AN:

25100

American (AMR)

AF:

0.000827

AC:

AN:

8462

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2576

East Asian (EAS)

AF:

0.00

AC:

AN:

2836

South Asian (SAS)

AF:

0.00

AC:

AN:

2554

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3284

Middle Eastern (MID)

AF:

0.00735

AC:

AN:

136

European-Non Finnish (NFE)

AF:

0.0000859

AC:

AN:

46590

Other (OTH)

AF:

0.000787

AC:

AN:

1270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.000245

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

0.56

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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