Genetic Variant NM_001271458.2:c.562G>T (chr11-111308243-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001271458.2(POU2AF3):c.562G>T(p.Ala188Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,551,452 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A188T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

POU2AF3
NM_001271458.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U: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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045202076).

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>T	p.Ala188Ser	missense	Exon 5 of 5	NP_001258387.1	A8K830-5
POU2AF3	NM_001136105.3		c.271G>T	p.Ala91Ser	missense	Exon 5 of 5	NP_001129577.1	A8K830-1
POU2AF3	NM_001271457.2		c.271G>T	p.Ala91Ser	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>T	p.Ala188Ser	missense	Exon 5 of 5	ENSP00000484135.1	A8K830-5
POU2AF3	ENST00000638573.1	TSL:1	c.667G>T	p.Ala223Ser	missense	Exon 6 of 6	ENSP00000492570.1	A8K830-4
POU2AF3	ENST00000398035.6	TSL:1	c.271G>T	p.Ala91Ser	missense	Exon 5 of 5	ENSP00000381115.2	A8K830-1

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000764

AC:

AN:

156976

AF XY:

0.0000722

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000131

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1399506

Hom.:

Cov.:

AF XY:

0.0000174

AC XY:

AN XY:

690248

show subpopulations

African (AFR)

AF:

0.0000316

AC:

AN:

31598

American (AMR)

AF:

0.000140

AC:

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.00

AC:

AN:

79234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

1078984

Other (OTH)

AF:

0.0000172

AC:

AN:

58042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

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:

0.0000461

AC:

AN:

151946

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41378

American (AMR)

AF:

0.000131

AC:

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000381

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

0.079

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.0070

(source)

DANN

Benign

0.57

DEOGEN2

Benign

0.031

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.61

M_CAP

Benign

0.0065

MetaRNN

Benign

0.045

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

PhyloP100

-2.6

PROVEAN

Benign

-1.6

REVEL

Benign

0.058

Sift

Benign

0.45

Sift4G

Benign

0.45

Polyphen

0.013

Vest4

0.13

MVP

0.030

ClinPred

0.031

GERP RS

-12

Varity_R

0.059

gMVP

0.033

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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