Variant chr1-151404932-G-T 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.4103C>A(p.Thr1368Asn) 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. 14/21 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: 1.61

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=0.08542317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POGZ	NM_015100.4 linkuse as main transcript	c.4103C>A	p.Thr1368Asn	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.4103C>A	p.Thr1368Asn	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

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2017

The p.T1368N variant (also known as c.4103C>A), located in coding exon 18 of the POGZ gene, results from a C to A substitution at nucleotide position 4103. The threonine at codon 1368 is replaced by asparagine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.020

.;T;.;.;.;.

Eigen

Benign

-0.20

Eigen_PC

Benign

0.0031

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.89

D;D;D;D;D;D

M_CAP

Benign

0.0044

MetaRNN

Benign

0.085

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;N;.;.;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.020

N;N;N;N;N;N

REVEL

Benign

0.052

Sift

Uncertain

0.028

D;D;D;D;D;D

Sift4G

Benign

0.12

T;T;T;T;T;T

Polyphen

0.036

B;B;B;.;.;B

Vest4

0.092

MutPred

0.12

.;Loss of phosphorylation at T1368 (P = 9e-04);.;.;.;.;

MVP

0.26

MPC

0.34

ClinPred

0.099

GERP RS

5.0

Varity_R

0.058

gMVP

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over