Variant 11-120305031-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014352.4(POU2F3):c.446C>T(p.Ala149Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000329 in 1,599,614 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00035 ( 1 hom. )

Consequence

POU2F3
NM_014352.4 missense, splice_region

Scores

Splicing: ADA: 0.9792

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.78

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU2F3	NM_014352.4 linkuse as main transcript	c.446C>T	p.Ala149Val	missense_variant, splice_region_variant	7/13	ENST00000543440.7	NP_055167.2	Q9UKI9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
POU2F3	ENST00000543440.7 linkuse as main transcript	c.446C>T	p.Ala149Val	missense_variant, splice_region_variant	7/13	1	NM_014352.4	ENSP00000441687.2	Q9UKI9-1
POU2F3	ENST00000533620.5 linkuse as main transcript	n.*112C>T		splice_region_variant, non_coding_transcript_exon_variant	8/14	1		ENSP00000435738.2	E9PIN6
POU2F3	ENST00000533620.5 linkuse as main transcript	n.*112C>T		3_prime_UTR_variant	8/14	1		ENSP00000435738.2	E9PIN6
POU2F3	ENST00000260264.8 linkuse as main transcript	c.452C>T	p.Ala151Val	missense_variant, splice_region_variant	7/13	2		ENSP00000260264.4	Q9UKI9-2

Frequencies

GnomAD3 genomes

AF:

0.000141

AC:

AN:

148590

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000500

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000281

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000246

AC:

AN:

248370

Hom.:

AF XY:

0.000261

AC XY:

AN XY:

134338

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000518

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000348

AC:

505

AN:

1451024

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

230

AN XY:

721718

show subpopulations

Gnomad4 AFR exome

AF:

0.0000601

Gnomad4 AMR exome

AF:

0.0000454

Gnomad4 ASJ exome

AF:

0.0000389

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000189

Gnomad4 NFE exome

AF:

0.000438

Gnomad4 OTH exome

AF:

0.000251

GnomAD4 genome

AF:

0.000141

AC:

AN:

148590

Hom.:

Cov.:

AF XY:

0.0000832

AC XY:

AN XY:

72146

show subpopulations

Gnomad4 AFR

AF:

0.0000500

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000281

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000383

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000305

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 15, 2021

The c.446C>T (p.A149V) alteration is located in exon 7 (coding exon 7) of the POU2F3 gene. This alteration results from a C to T substitution at nucleotide position 446, causing the alanine (A) at amino acid position 149 to be replaced by a valine (V). 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

0.096

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

.;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.17

T;T

MetaSVM

Uncertain

0.019

MutationAssessor

Benign

2.0

.;M

PrimateAI

Uncertain

0.65

REVEL

Uncertain

0.34

Sift4G

Uncertain

0.051

T;T

Polyphen

0.84

.;P

Vest4

0.29

MVP

0.72

MPC

0.65

ClinPred

0.63

GERP RS

6.2

Varity_R

0.19

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Pathogenic

0.79

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