7-39451627-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001370959.1(POU6F2):​c.1415C>T​(p.Pro472Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

POU6F2
NM_001370959.1 missense

Scores

3
12
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.64
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
POU6F2NM_001370959.1 linkc.1415C>T p.Pro472Leu missense_variant Exon 8 of 10 ENST00000518318.7 NP_001357888.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
POU6F2ENST00000518318.7 linkc.1415C>T p.Pro472Leu missense_variant Exon 8 of 10 1 NM_001370959.1 ENSP00000430514.3 A0A6E1XZL4

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152200
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250126
Hom.:
0
AF XY:
0.00000740
AC XY:
1
AN XY:
135082
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1328C>T (p.P443L) alteration is located in exon 9 (coding exon 8) of the POU6F2 gene. This alteration results from a C to T substitution at nucleotide position 1328, causing the proline (P) at amino acid position 443 to be replaced by a leucine (L). 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
0.24
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Uncertain
0.080
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.54
D;.;.;.
Eigen
Uncertain
0.62
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.95
D;D;D;D
M_CAP
Benign
0.050
D
MetaRNN
Uncertain
0.52
D;D;D;D
MetaSVM
Uncertain
-0.21
T
MutationAssessor
Benign
0.81
L;L;.;.
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-2.4
N;N;N;N
REVEL
Uncertain
0.31
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Uncertain
0.0080
D;D;D;D
Polyphen
1.0
D;.;.;.
Vest4
0.68
MVP
0.96
MPC
0.13
ClinPred
0.86
D
GERP RS
5.7
Varity_R
0.26
gMVP
0.84

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.

Other links and lift over

dbSNP: rs202234462; hg19: chr7-39491226; COSMIC: COSV101302642; API