dbSNP rs1553426334: POU3F3:p.Pro102Leu (chr2-104855815-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_006236.3(POU3F3):c.305C>T(p.Pro102Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

POU3F3
NM_006236.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 12 curated pathogenic missense variants (we use a threshold of 10). The gene has 2 curated benign missense variants. Gene score misZ: 3.0416 (below the threshold of 3.09). Trascript score misZ: -0.11043 (below the threshold of 3.09). GenCC associations: The gene is linked to snijders blok-fisher syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.37211442).

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.305C>T	p.Pro102Leu	missense	Exon 1 of 1	NP_006227.1	P20264
POU3F3	NM_001433704.1		c.305C>T	p.Pro102Leu	missense	Exon 2 of 2	NP_001420633.1	P20264
POU3F3	NR_197431.1		n.294+2246C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POU3F3	ENST00000361360.4	TSL:6 MANE Select	c.305C>T	p.Pro102Leu	missense	Exon 1 of 1	ENSP00000355001.2	P20264
POU3F3	ENST00000674056.1		c.305C>T	p.Pro102Leu	missense	Exon 4 of 4	ENSP00000501036.1	P20264
ENSG00000269707	ENST00000598623.1	TSL:5	n.345+1983C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1041100

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

509578

African (AFR)

AF:

0.00

AC:

AN:

19668

American (AMR)

AF:

0.00

AC:

AN:

11012

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11886

East Asian (EAS)

AF:

0.00

AC:

AN:

14510

South Asian (SAS)

AF:

0.00

AC:

AN:

42186

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15398

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2954

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

886734

Other (OTH)

AF:

0.00

AC:

AN:

36752

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.0091

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.21

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.45

LIST_S2

Uncertain

0.88

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.37

MetaSVM

Uncertain

-0.14

MutationAssessor

Benign

1.1

PhyloP100

3.2

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.30

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0050

Polyphen

0.99

Vest4

0.24

MutPred

0.38

Loss of glycosylation at P102 (P = 0.0214)

MVP

0.75

ClinPred

0.79

GERP RS

0.57

Varity_R

0.16

gMVP

0.31

Mutation Taster

=63/37

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over