dbSNP rs151083714: POU2F3:p.Phe150Ser (chr11-120305034-T-C) – 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.449T>C(p.Phe150Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000249 in 1,604,848 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

POU2F3
NM_014352.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.75

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=0.06203264).

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.449T>C	p.Phe150Ser	missense	Exon 7 of 13	NP_055167.2	Q9UKI9-1
	POU2F3	NM_001244682.2		c.455T>C	p.Phe152Ser	missense	Exon 7 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.449T>C	p.Phe150Ser	missense	Exon 7 of 13	ENSP00000441687.2	Q9UKI9-1
POU2F3	ENST00000533620.5	TSL:1	n.*115T>C		non_coding_transcript_exon	Exon 8 of 14	ENSP00000435738.2	E9PIN6
POU2F3	ENST00000533620.5	TSL:1	n.*115T>C		3_prime_UTR	Exon 8 of 14	ENSP00000435738.2	E9PIN6

Frequencies

GnomAD3 genomes

AF:

0.000133

AC:

AN:

150778

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000733

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000664

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:

0.000236

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000161

AC:

AN:

248994

AF XY:

0.000163

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000588

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000320

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000261

AC:

379

AN:

1454070

Hom.:

Cov.:

AF XY:

0.000252

AC XY:

182

AN XY:

723252

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33348

American (AMR)

AF:

0.0000453

AC:

AN:

44164

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25808

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

85106

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53000

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.000317

AC:

351

AN:

1107314

Other (OTH)

AF:

0.000367

AC:

AN:

59950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

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:

0.000133

AC:

AN:

150778

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

73520

show subpopulations

African (AFR)

AF:

0.0000733

AC:

AN:

40910

American (AMR)

AF:

0.0000664

AC:

AN:

15054

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4722

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.000236

AC:

AN:

67820

Other (OTH)

AF:

0.00

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.000612

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000214

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

0.072

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.049

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.30

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.17

M_CAP

Benign

0.0060

MetaRNN

Benign

0.062

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.34

PhyloP100

4.7

PrimateAI

Benign

0.35

REVEL

Benign

0.21

Sift4G

Benign

0.79

Polyphen

0.0

Vest4

0.16

MVP

0.61

MPC

0.40

ClinPred

0.093

GERP RS

3.9

Varity_R

0.079

gMVP

0.26

Mutation Taster

=99/1

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