Genetic Variant POU2F3:p.Phe150Ser (chr11-120305034-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. 12/19 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

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06203264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU2F3	NM_014352.4 link	c.449T>C	p.Phe150Ser	missense_variant	Exon 7 of 13	ENST00000543440.7	NP_055167.2	Q9UKI9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
POU2F3	ENST00000543440.7 link	c.449T>C	p.Phe150Ser	missense_variant	Exon 7 of 13	1	NM_014352.4	ENSP00000441687.2	Q9UKI9-1
POU2F3	ENST00000533620.5 link	n.*115T>C		non_coding_transcript_exon_variant	Exon 8 of 14	1		ENSP00000435738.2	E9PIN6
POU2F3	ENST00000533620.5 link	n.*115T>C		3_prime_UTR_variant	Exon 8 of 14	1		ENSP00000435738.2	E9PIN6
POU2F3	ENST00000260264.8 link	c.455T>C	p.Phe152Ser	missense_variant	Exon 7 of 13	2		ENSP00000260264.4	Q9UKI9-2

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

GnomAD3 exomes

AF:

0.000161

AC:

AN:

248994

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

134676

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 SAS 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

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000453

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000317

Gnomad4 OTH exome

AF:

0.000367

GnomAD4 genome

AF:

0.000133

AC:

AN:

150778

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

73520

show subpopulations

Gnomad4 AFR

AF:

0.0000733

Gnomad4 AMR

AF:

0.0000664

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000236

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000687

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000214

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 26, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.449T>C (p.F150S) alteration is located in exon 7 (coding exon 7) of the POU2F3 gene. This alteration results from a T to C substitution at nucleotide position 449, causing the phenylalanine (F) at amino acid position 150 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.049

.;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.30

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.17

T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.062

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.34

.;N

PrimateAI

Benign

0.35

REVEL

Benign

0.21

Sift4G

Benign

0.79

T;T

Polyphen

0.0

.;B

Vest4

0.16

MVP

0.61

MPC

0.40

ClinPred

0.093

GERP RS

3.9

Varity_R

0.079

gMVP

0.26

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over