7-39207456-C-T

Position:

• chr7-39207456-C-T

Variant summary

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

The NM_001370959.1(POU6F2):​c.434C>T​(p.Ala145Val) 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: 33)
• Consequence: POU6F2 NM_001370959.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.24

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU6F2	NM_001370959.1	c.434C>T	p.Ala145Val	missense_variant	4/10	ENST00000518318.7	NP_001357888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU6F2	ENST00000518318.7	c.434C>T	p.Ala145Val	missense_variant	4/10	1	NM_001370959.1	ENSP00000430514	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Sep 01, 2021

The c.347C>T (p.A116V) alteration is located in exon 5 (coding exon 4) of the POU6F2 gene. This alteration results from a C to T substitution at nucleotide position 347, causing the alanine (A) at amino acid position 116 to be replaced by a valine (V). 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	0.10
BayesDel_addAF	Uncertain	0.088	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.;.;.;.;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T;T;D;D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.46	T;T;T;T;T;T
MetaSVM	Uncertain	0.099	D
MutationAssessor	Benign	0.69	N;N;.;.;.;.
MutationTaster	Benign	0.52	N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.0	N;N;D;N;N;N
REVEL	Uncertain	0.39
Sift	Uncertain	0.0020	D;D;D;D;D;D
Sift4G	Uncertain	0.019	D;D;D;T;T;T
Polyphen		0.38	B;P;.;.;.;.
Vest4		0.62
MutPred		0.28		Loss of disorder (P = 0.0809);Loss of disorder (P = 0.0809);.;.;.;.;
MVP		0.94
MPC		0.44
ClinPred		0.91	D
GERP RS		6.2
Varity_R		0.19
gMVP		0.44

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: chr7-39247055; COSMIC: COSV68870284;