dbSNP rs201045815: POU2AF3:p.Pro176Gln (chr11-111308208-C-A) – 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_001271458.2(POU2AF3):c.527C>A(p.Pro176Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,551,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

POU2AF3
NM_001271458.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.338

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:

Genome browser will be placed here

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=0.03778416).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU2AF3	NM_001271458.2 link	c.527C>A	p.Pro176Gln	missense_variant	Exon 5 of 5	ENST00000610738.6	NP_001258387.1	A8K830-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU2AF3	ENST00000610738.6 link	c.527C>A	p.Pro176Gln	missense_variant	Exon 5 of 5	1	NM_001271458.2	ENSP00000484135.1		A8K830-5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000254

AC:

AN:

157260

Hom.:

AF XY:

0.0000241

AC XY:

AN XY:

83140

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000917

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000328

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1399532

Hom.:

Cov.:

AF XY:

0.0000174

AC XY:

AN XY:

690264

show subpopulations

Gnomad4 AFR exome

AF:

0.0000633

Gnomad4 AMR exome

AF:

0.00

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:

0.0000158

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0000962

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000225

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000383

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.41

CADD

Benign

9.1

DANN

Uncertain

0.97

DEOGEN2

Benign

0.076

.;.;.;T;T;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.52

T;T;T;T;.;.

M_CAP

Benign

0.0045

MetaRNN

Benign

0.038

T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.14

.;.;.;N;N;N

PROVEAN

Benign

-1.9

.;.;N;.;N;N

REVEL

Benign

0.11

Sift

Benign

0.27

.;.;T;.;T;T

Sift4G

Uncertain

0.020

D;.;T;T;T;T

Polyphen

0.091

.;.;.;B;B;B

Vest4

0.14

MutPred

0.12

.;.;Loss of catalytic residue at P78 (P = 0.016);Loss of catalytic residue at P78 (P = 0.016);Loss of catalytic residue at P78 (P = 0.016);Loss of catalytic residue at P78 (P = 0.016);

MVP

0.030

ClinPred

0.018

GERP RS

5.0

Varity_R

0.050

gMVP

0.058

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over