dbSNP rs776644128: POU2AF3:p.Ala188Thr (chr11-111308243-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001271458.2(POU2AF3):c.562G>A(p.Ala188Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,551,570 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A188S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000052 ( 2 hom. )

Consequence

POU2AF3
NM_001271458.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.63

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022285491).

BP6

Variant 11-111308243-G-A is Benign according to our data. Variant chr11-111308243-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2599663.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271458.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POU2AF3	NM_001271458.2	MANE Select	c.562G>A	p.Ala188Thr	missense	Exon 5 of 5	NP_001258387.1	A8K830-5
POU2AF3	NM_001136105.3		c.271G>A	p.Ala91Thr	missense	Exon 5 of 5	NP_001129577.1	A8K830-1
POU2AF3	NM_001271457.2		c.271G>A	p.Ala91Thr	missense	Exon 5 of 5	NP_001258386.1	A8K830-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POU2AF3	ENST00000610738.6	TSL:1 MANE Select	c.562G>A	p.Ala188Thr	missense	Exon 5 of 5	ENSP00000484135.1	A8K830-5
POU2AF3	ENST00000638573.1	TSL:1	c.667G>A	p.Ala223Thr	missense	Exon 6 of 6	ENSP00000492570.1	A8K830-4
POU2AF3	ENST00000398035.6	TSL:1	c.271G>A	p.Ala91Thr	missense	Exon 5 of 5	ENSP00000381115.2	A8K830-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000108

AC:

AN:

156976

AF XY:

0.000108

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000681

GnomAD4 exome

AF:

0.0000522

AC:

AN:

1399506

Hom.:

Cov.:

AF XY:

0.0000594

AC XY:

AN XY:

690248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31598

American (AMR)

AF:

0.0000560

AC:

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.000199

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.000480

AC:

AN:

79234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49326

Middle Eastern (MID)

AF:

0.00140

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.0000139

AC:

AN:

1078984

Other (OTH)

AF:

0.0000861

AC:

AN:

58042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152064

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41500

American (AMR)

AF:

0.000197

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67986

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.000153

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.0080

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.028

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.66

M_CAP

Benign

0.0023

MetaRNN

Benign

0.022

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.17

PhyloP100

-2.6

PROVEAN

Benign

-1.4

REVEL

Benign

0.042

Sift

Benign

0.67

Sift4G

Benign

0.59

Polyphen

0.0030

Vest4

0.083

MutPred

0.26

Gain of glycosylation at A91 (P = 0.0431)

MVP

0.030

ClinPred

0.016

GERP RS

-12

Varity_R

0.030

gMVP

0.035

Mutation Taster

=100/0

polymorphism

(source)

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over