Variant chr7-39204319-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001370959.1(POU6F2):c.362G>A(p.Gly121Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,612,690 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

POU6F2
NM_001370959.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 8.31

Variant links:

Genes affected

POU6F2 (HGNC:21694): (POU class 6 homeobox 2) This gene encodes a member of the POU protein family characterized by the presence of a bipartite DNA binding domain, consisting of a POU-specific domain and a homeodomain, separated by a variable polylinker. The DNA binding domain may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner. The POU family members are transcriptional regulators, many of which are known to control cell type-specific differentiation pathways. This gene is a tumor suppressor involved in Wilms tumor (WT) predisposition. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

POU6F2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU6F2	NM_001370959.1 linkuse as main transcript	c.362G>A	p.Gly121Glu	missense_variant	3/10	ENST00000518318.7	NP_001357888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU6F2	ENST00000518318.7 linkuse as main transcript	c.362G>A	p.Gly121Glu	missense_variant	3/10	1	NM_001370959.1	ENSP00000430514	P2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151942

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250638

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135444

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1460748

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726688

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000990

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151942

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.275G>A (p.G92E) alteration is located in exon 4 (coding exon 3) of the POU6F2 gene. This alteration results from a G to A substitution at nucleotide position 275, causing the glycine (G) at amino acid position 92 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Hypogonadotropic hypogonadism

Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Department of Pediatric Endocrinology, Cukurova University Medical Faculty

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.34

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.;.;.;.;.

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.79

T;T;D;D;D;D

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.69

D;D;D;D;D;D

MetaSVM

Uncertain

0.54

MutationAssessor

Benign

0.81

L;L;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.3

N;N;N;N;N;N

REVEL

Uncertain

0.51

Sift

Uncertain

0.0040

D;D;D;D;D;D

Sift4G

Uncertain

0.0090

D;D;D;T;D;D

Polyphen

1.0

D;D;.;.;.;.

Vest4

0.92

MutPred

0.30

Gain of glycosylation at P90 (P = 0.1058);Gain of glycosylation at P90 (P = 0.1058);.;.;.;.;

MVP

0.98

MPC

0.66

ClinPred

0.90

GERP RS

5.8

Varity_R

0.25

gMVP

0.45

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