NM_001370959.1:c.119C>G

Variant names:

• chr7-39085873-C-G
• rs759457081
• NM_001370959.1:c.119C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001370959.1(POU6F2):​c.119C>G​(p.Ala40Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: POU6F2 NM_001370959.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.23

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34351227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU6F2	NM_001370959.1	c.119C>G	p.Ala40Gly	missense_variant	Exon 2 of 10	ENST00000518318.7	NP_001357888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU6F2	ENST00000518318.7	c.119C>G	p.Ala40Gly	missense_variant	Exon 2 of 10	1	NM_001370959.1	ENSP00000430514.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;.;.;.;.;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.77	T;T;D;T;D;D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.34	T;T;T;T;T;T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	0.34	N;N;.;.;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.6	N;N;N;N;N;N
REVEL	Uncertain	0.34
Sift	Uncertain	0.0080	D;D;D;D;D;D
Sift4G	Uncertain	0.036	D;D;D;D;D;D
Polyphen		0.62	P;D;.;.;.;.
Vest4		0.45
MutPred		0.063		Gain of methylation at K16 (P = 0.1374);Gain of methylation at K16 (P = 0.1374);.;.;.;.;
MVP		0.94
MPC		0.57
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.35
gMVP		0.091

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs759457081; hg19: chr7-39125473;