Genetic Variant POU6F2:p.Gly438Ser (chr7-39433275-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001370959.1(POU6F2):c.1312G>A(p.Gly438Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,613,908 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. G438G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

POU6F2
NM_001370959.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 10.0

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:

LOC105375238 (HGNC:):

LOC105375238 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011610687).

BP6

Variant 7-39433275-G-A is Benign according to our data. Variant chr7-39433275-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 785213.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 207 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU6F2	NM_001370959.1 link	c.1312G>A	p.Gly438Ser	missense_variant	Exon 7 of 10	ENST00000518318.7	NP_001357888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU6F2	ENST00000518318.7 link	c.1312G>A	p.Gly438Ser	missense_variant	Exon 7 of 10	1	NM_001370959.1	ENSP00000430514.3		A0A6E1XZL4

Frequencies

GnomAD3 genomes

AF:

0.00136

AC:

207

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00468

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000323

AC:

AN:

250534

Hom.:

AF XY:

0.000222

AC XY:

AN XY:

135404

show subpopulations

Gnomad AFR exome

AF:

0.00407

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000119

AC:

174

AN:

1461664

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.00358

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.00136

AC:

207

AN:

152244

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00467

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000216

Hom.:

Bravo

AF:

0.00145

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000420

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Pathogenic

0.27

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.096

T;.;.;.;.

Eigen

Pathogenic

0.71

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

D;D;D;D;D

M_CAP

Benign

0.050

MetaRNN

Benign

0.012

T;T;T;T;T

MetaSVM

Uncertain

0.057

MutationAssessor

Benign

0.81

L;L;.;.;.

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.15

N;N;N;N;N

REVEL

Uncertain

0.44

Sift

Uncertain

0.0060

D;D;D;D;D

Sift4G

Benign

0.36

T;T;T;D;T

Polyphen

1.0

D;.;.;.;.

Vest4

0.75

MVP

0.95

MPC

0.13

ClinPred

0.083

GERP RS

5.6

Varity_R

0.13

gMVP

0.56

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