dbSNP rs368929654: POU6F2:p.Ser390Arg (chr7-39433133-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001370959.1(POU6F2):c.1170C>A(p.Ser390Arg) variant causes a missense change involving the alteration of a non-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. Synonymous variant affecting the same amino acid position (i.e. S390S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

POU6F2
NM_001370959.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.51

Publications

0 publications found

Variant links:

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 links:

YAE1-DT (HGNC:55820): (YAE1 divergent transcript)

YAE1-DT links:

LOC105375238 (HGNC:):

LOC105375238 links:

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ACMG classification

Classification was made for transcript

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=0.15584102).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POU6F2	NM_001370959.1	MANE Select	c.1170C>A	p.Ser390Arg	missense	Exon 7 of 10	NP_001357888.1	A0A6E1XZL4
POU6F2	NM_007252.4		c.1083C>A	p.Ser361Arg	missense	Exon 8 of 11	NP_009183.3	P78424-1
POU6F2	NM_001166018.2		c.1083C>A	p.Ser361Arg	missense	Exon 8 of 11	NP_001159490.1	P78424-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POU6F2	ENST00000518318.7	TSL:1 MANE Select	c.1170C>A	p.Ser390Arg	missense	Exon 7 of 10	ENSP00000430514.3	A0A6E1XZL4
POU6F2	ENST00000403058.6	TSL:5	c.1083C>A	p.Ser361Arg	missense	Exon 8 of 11	ENSP00000384004.1	P78424-1
POU6F2	ENST00000416452.1	TSL:5	n.180C>A		non_coding_transcript_exon	Exon 2 of 4	ENSP00000404868.1	H7C2B2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

0.0085

BayesDel_noAF

Benign

-0.23

CADD

Benign

0.71

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.16

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.055

LIST_S2

Uncertain

0.88

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.47

MutationAssessor

Benign

0.55

PhyloP100

-1.5

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.43

Sift

Uncertain

0.0050

Sift4G

Benign

0.51

Polyphen

0.80

Vest4

0.53

MutPred

0.19

Loss of glycosylation at S361 (P = 0.0037)

MVP

0.60

MPC

0.14

ClinPred

0.40

GERP RS

-11

Varity_R

0.15

gMVP

0.67

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over