7-39085960-G-A

Position:

• chr7-39085960-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370959.1(POU6F2):​c.206G>A​(p.Ser69Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: POU6F2 NM_001370959.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.73

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22613546).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU6F2	NM_001370959.1	c.206G>A	p.Ser69Asn	missense_variant	2/10	ENST00000518318.7	NP_001357888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU6F2	ENST00000518318.7	c.206G>A	p.Ser69Asn	missense_variant	2/10	1	NM_001370959.1	ENSP00000430514	P2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2024

The c.119G>A (p.S40N) alteration is located in exon 3 (coding exon 2) of the POU6F2 gene. This alteration results from a G to A substitution at nucleotide position 119, causing the serine (S) at amino acid position 40 to be replaced by an asparagine (N). 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	0.068
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.071	T;.;.;.;.;.
Eigen	Benign	-0.014
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.68	T;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.23	T;T;T;T;T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.69	N;N;.;.;.;.
MutationTaster	Benign	0.93	N;N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.48	N;N;N;N;N;N
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D;D;T;T;T;D
Sift4G	Benign	0.36	T;T;T;T;T;T
Polyphen		0.0040	B;B;.;.;.;.
Vest4		0.18
MutPred		0.15		Loss of phosphorylation at S40 (P = 0.0176);Loss of phosphorylation at S40 (P = 0.0176);.;.;.;.;
MVP		0.86
MPC		0.14
ClinPred		0.60	D
GERP RS		4.3
Varity_R		0.26
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-39125560;