NM_001370959.1:c.148G>C

Variant names:

• chr7-39085902-G-C
• NM_001370959.1:c.148G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370959.1(POU6F2):​c.148G>C​(p.Val50Leu) 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. 13/22 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: 6.15
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Wilms tumor 5

  Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14269).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370959.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU6F2	NM_001370959.1	MANE Select	c.148G>C	p.Val50Leu	missense	Exon 2 of 10	NP_001357888.1	A0A6E1XZL4
	POU6F2	NM_007252.4		c.61G>C	p.Val21Leu	missense	Exon 3 of 11	NP_009183.3	P78424-1
	POU6F2	NM_001166018.2		c.61G>C	p.Val21Leu	missense	Exon 3 of 11	NP_001159490.1	P78424-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU6F2	ENST00000518318.7	TSL:1 MANE Select	c.148G>C	p.Val50Leu	missense	Exon 2 of 10	ENSP00000430514.3	A0A6E1XZL4
	POU6F2	ENST00000403058.6	TSL:5	c.61G>C	p.Val21Leu	missense	Exon 3 of 11	ENSP00000384004.1	P78424-1
	POU6F2	ENST00000451021.5	TSL:4	n.200G>C		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.27
Eigen_PC	Benign	0.0020
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	-0.20	N
PhyloP100		6.2
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.39	N
REVEL	Uncertain	0.30
Sift	Benign	0.35	T
Sift4G	Benign	0.71	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.090		Loss of catalytic residue at V21 (P = 0.0094)
MVP		0.75
MPC		0.13
ClinPred		0.86	D
GERP RS		4.5
Varity_R		0.19
gMVP		0.073
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

hg19: chr7-39125502;