NM_001370959.1:c.638T>G

Variant names:

• chr7-39339681-T-G
• rs566759150
• NM_001370959.1:c.638T>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001370959.1(POU6F2):​c.638T>G​(p.Leu213Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000987 in 1,601,858 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00095 (1 hom.)
• Consequence: POU6F2 NM_001370959.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 6.37

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008406937).
• BP6: Variant 7-39339681-T-G is Benign according to our data. Variant chr7-39339681-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 713595.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 201 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU6F2	NM_001370959.1	c.638T>G	p.Leu213Arg	missense_variant	Exon 5 of 10	ENST00000518318.7	NP_001357888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU6F2	ENST00000518318.7	c.638T>G	p.Leu213Arg	missense_variant	Exon 5 of 10	1	NM_001370959.1	ENSP00000430514.3

Frequencies

GnomAD3 genomes AF: 0.00132 AC: 200 AN: 151944 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000853

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00748

Gnomad FIN AF: 0.00368

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00144

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000795 AC: 187 AN: 235256 Hom.: 1 AF XY: 0.000975 AC XY: 125 AN XY: 128164

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000263

Gnomad ASJ exome AF: 0.000627

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00371

Gnomad FIN exome AF: 0.00149

Gnomad NFE exome AF: 0.000309

Gnomad OTH exome AF: 0.00102

GnomAD4 exome AF: 0.000952 AC: 1380 AN: 1449796 Hom.: 1 Cov.: 32 AF XY: 0.00115 AC XY: 832 AN XY: 721262

Gnomad4 AFR exome AF: 0.000120

Gnomad4 AMR exome AF: 0.000583

Gnomad4 ASJ exome AF: 0.000695

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00641

Gnomad4 FIN exome AF: 0.00214

Gnomad4 NFE exome AF: 0.000560

Gnomad4 OTH exome AF: 0.000864

GnomAD4 genome AF: 0.00132 AC: 201 AN: 152062 Hom.: 1 Cov.: 32 AF XY: 0.00152 AC XY: 113 AN XY: 74346

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.000852

Gnomad4 ASJ AF: 0.000866

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00770

Gnomad4 FIN AF: 0.00368

Gnomad4 NFE AF: 0.00144

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000674 Hom.: 0

ExAC AF: 0.000548 AC: 66

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 17, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

POU6F2-related disorder Benign:1

Apr 12, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T;.;.;.;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.48	T;T;T;T;T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.0084	T;T;T;T;T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	0.34	N;N;.;.;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.27	N;N;N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.050	D;D;T;D;D
Sift4G	Benign	0.38	T;T;T;T;T
Polyphen		0.99	D;D;.;.;.
Vest4		0.71
MVP		0.90
MPC		0.19
ClinPred		0.079	T
GERP RS		4.5
Varity_R		0.31
gMVP		0.14

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

Other links and lift over

dbSNP: rs566759150; hg19: chr7-39379280;