Genetic Variant POU2AF3:p.Thr13Ser (chr11-111299815-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000638573.1(POU2AF3):c.37A>T(p.Thr13Ser) 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. 8/9 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

POU2AF3
ENST00000638573.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0170

Publications

11 publications found

Variant links:

Genes affected

POU2AF3 (HGNC:26978): (POU class 2 homeobox associating factor 3) Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

POU2AF3 links:

COLCA1 (HGNC:33789): (colorectal cancer associated 1) This gene encodes a transmembrane protein that localizes to granular structures, including crystalloid eosinophilic granules and other granular organelles. This gene, along with an overlapping opposite strand gene, has been implicated as a susceptibility locus for colorectal cancer. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Nov 2014]

COLCA1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.107586235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU2AF3	NM_001271458.2 link	c.8-712A>T		intron_variant	Intron 1 of 4	ENST00000610738.6	NP_001258387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU2AF3	ENST00000610738.6 link	c.8-712A>T		intron_variant	Intron 1 of 4	1	NM_001271458.2	ENSP00000484135.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

798072

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

383078

African (AFR)

AF:

0.00

AC:

AN:

17536

American (AMR)

AF:

0.00

AC:

AN:

8112

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12626

East Asian (EAS)

AF:

0.00

AC:

AN:

25298

South Asian (SAS)

AF:

0.00

AC:

AN:

14018

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21170

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2446

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

662200

Other (OTH)

AF:

0.00

AC:

AN:

34666

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.1

(source)

DANN

Benign

0.76

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.14

MetaRNN

Benign

0.11

PhyloP100

0.017

GERP RS

-5.7

PromoterAI

-0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over