dbSNP rs143843036: POU2F3:p.Ser147Thr (chr11-120302363-T-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014352.4(POU2F3):c.439T>A(p.Ser147Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000587 in 1,601,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

POU2F3
NM_014352.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.04

Publications

2 publications found

Variant links:

Genes affected

POU2F3 (HGNC:19864): (POU class 2 homeobox 3) This gene encodes a member of the POU domain family of transcription factors. POU domain transcription factors bind to a specific octamer DNA motif and regulate cell type-specific differentiation pathways. The encoded protein is primarily expressed in the epidermis, and plays a critical role in keratinocyte proliferation and differentiation. The encoded protein is also a candidate tumor suppressor protein, and aberrant promoter methylation of this gene may play a role in cervical cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

POU2F3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.051953524).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014352.4. 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
	POU2F3	NM_014352.4	MANE Select	c.439T>A	p.Ser147Thr	missense	Exon 6 of 13	NP_055167.2	Q9UKI9-1
	POU2F3	NM_001244682.2		c.445T>A	p.Ser149Thr	missense	Exon 6 of 13	NP_001231611.1	Q9UKI9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POU2F3	ENST00000543440.7	TSL:1 MANE Select	c.439T>A	p.Ser147Thr	missense	Exon 6 of 13	ENSP00000441687.2	Q9UKI9-1
POU2F3	ENST00000533620.5	TSL:1	n.*105T>A		non_coding_transcript_exon	Exon 7 of 14	ENSP00000435738.2	E9PIN6
POU2F3	ENST00000533620.5	TSL:1	n.*105T>A		3_prime_UTR	Exon 7 of 14	ENSP00000435738.2	E9PIN6

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000837

AC:

AN:

250984

AF XY:

0.0000516

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.0000872

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:

0.0000359

AC:

AN:

1449402

Hom.:

Cov.:

AF XY:

0.0000360

AC XY:

AN XY:

721838

show subpopulations

African (AFR)

AF:

0.00133

AC:

AN:

33152

American (AMR)

AF:

0.0000895

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26070

East Asian (EAS)

AF:

0.00

AC:

AN:

39648

South Asian (SAS)

AF:

0.00

AC:

AN:

85946

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1100740

Other (OTH)

AF:

0.0000167

AC:

AN:

60002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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:

0.000276

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.000962

AC:

AN:

41570

American (AMR)

AF:

0.0000654

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.0000503

Hom.:

Bravo

AF:

0.000272

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.049

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.69

M_CAP

Benign

0.035

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.35

MutationAssessor

Benign

1.1

PhyloP100

3.0

PrimateAI

Uncertain

0.52

REVEL

Benign

0.24

Sift4G

Benign

1.0

Polyphen

0.99

Vest4

0.49

MVP

0.73

MPC

0.76

ClinPred

0.075

GERP RS

6.0

Varity_R

0.13

gMVP

0.40

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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