Variant 1-151404933-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 5P and 2B. PM1PM2PP2BP4_Moderate

The NM_015100.4(POGZ):c.4102A>T(p.Thr1368Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1368K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

POGZ
NM_015100.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.73

Variant links:

Genes affected

POGZ (HGNC:18801): (pogo transposable element derived with ZNF domain) The protein encoded by this gene appears to be a zinc finger protein containing a transposase domain at the C-terminus. This protein was found to interact with the transcription factor SP1 in a yeast two-hybrid system. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Aug 2010]

POGZ links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM1

In a modified_residue Phosphothreonine (size 0) in uniprot entity POGZ_HUMAN

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), POGZ. . Gene score misZ 3.5062 (greater than the threshold 3.09). Trascript score misZ 4.1346 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40, intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.089532495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POGZ	NM_015100.4 linkuse as main transcript	c.4102A>T	p.Thr1368Ser	missense_variant	19/19	ENST00000271715.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POGZ	ENST00000271715.7 linkuse as main transcript	c.4102A>T	p.Thr1368Ser	missense_variant	19/19	1	NM_015100.4	P3	Q7Z3K3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2019

Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; In silico predictors and evolutionary conservation suggest the missense change does not alter protein structure/function -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.020

.;T;.;.;.;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.82

T;T;T;T;T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.090

T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

.;N;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

0.010

N;N;N;N;N;N

REVEL

Benign

0.049

Sift

Benign

0.036

D;T;D;T;T;D

Sift4G

Benign

0.16

T;T;T;T;T;T

Polyphen

0.0040

B;B;B;.;.;B

Vest4

0.19

MutPred

0.15

.;Loss of glycosylation at T1368 (P = 0.0642);.;.;.;.;

MVP

0.26

MPC

0.29

ClinPred

0.067

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.030

gMVP

0.39

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over