Variant 11-111306577-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001271458.2(POU2AF3):c.341T>G(p.Phe114Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,551,732 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00083 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 1 hom. )

Consequence

POU2AF3
NM_001271458.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.487

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044735163).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU2AF3	NM_001271458.2 linkuse as main transcript	c.341T>G	p.Phe114Cys	missense_variant	4/5	ENST00000610738.6	NP_001258387.1	A8K830-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU2AF3	ENST00000610738.6 linkuse as main transcript	c.341T>G	p.Phe114Cys	missense_variant	4/5	1	NM_001271458.2	ENSP00000484135.1		A8K830-5

Frequencies

GnomAD3 genomes

AF:

0.000835

AC:

127

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000739

AC:

116

AN:

156964

Hom.:

AF XY:

0.000722

AC XY:

AN XY:

83066

show subpopulations

Gnomad AFR exome

AF:

0.000375

Gnomad AMR exome

AF:

0.000284

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000966

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00133

Gnomad OTH exome

AF:

0.000454

GnomAD4 exome

AF:

0.00150

AC:

2098

AN:

1399448

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

1039

AN XY:

690230

show subpopulations

Gnomad4 AFR exome

AF:

0.000316

Gnomad4 AMR exome

AF:

0.000280

Gnomad4 ASJ exome

AF:

0.0000397

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000947

Gnomad4 FIN exome

AF:

0.0000811

Gnomad4 NFE exome

AF:

0.00181

Gnomad4 OTH exome

AF:

0.000827

GnomAD4 genome

AF:

0.000834

AC:

127

AN:

152284

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.000903

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00156

AC:

ExAC

AF:

0.000598

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 28, 2022

The c.50T>G (p.F17C) alteration is located in exon 4 (coding exon 1) of the COLCA2 gene. This alteration results from a T to G substitution at nucleotide position 50, causing the phenylalanine (F) at amino acid position 17 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

.;.;.;T;T;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.58

T;T;T;T;.;.

M_CAP

Benign

0.0037

MetaRNN

Benign

0.045

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;.;.;L;L;L

PROVEAN

Pathogenic

-6.9

.;.;D;.;D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.0010

.;.;D;.;D;D

Sift4G

Uncertain

0.0070

D;.;D;D;D;D

Polyphen

0.051

.;.;.;B;B;B

Vest4

0.25

MVP

0.13

ClinPred

0.043

GERP RS

4.7

Varity_R

0.25

gMVP

0.16

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over