Genetic Variant NM_015100.4:c.4154A>G (chr1-151404881-T-C) – 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_015100.4(POGZ):c.4154A>G(p.His1385Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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. H1385Y) 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: 6.89

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Illumina

POGZ 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=0.16530293).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015100.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POGZ	NM_015100.4	MANE Select	c.4154A>G	p.His1385Arg	missense	Exon 19 of 19	NP_055915.2
POGZ	NM_001410860.1		c.4175A>G	p.His1392Arg	missense	Exon 19 of 19	NP_001397789.1	A0A8V8TQ67
POGZ	NM_001194937.2		c.4127A>G	p.His1376Arg	missense	Exon 19 of 19	NP_001181866.1	Q7Z3K3-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POGZ	ENST00000271715.7	TSL:1 MANE Select	c.4154A>G	p.His1385Arg	missense	Exon 19 of 19	ENSP00000271715.2	Q7Z3K3-1
POGZ	ENST00000392723.6	TSL:1	c.3995A>G	p.His1332Arg	missense	Exon 18 of 18	ENSP00000376484.1	Q7Z3K3-2
POGZ	ENST00000368863.6	TSL:1	c.3869A>G	p.His1290Arg	missense	Exon 17 of 17	ENSP00000357856.2	Q7Z3K3-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.022

Eigen

Benign

-0.060

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.0030

MetaRNN

Benign

0.17

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

6.9

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.74

REVEL

Benign

0.15

Sift

Uncertain

0.020

Sift4G

Benign

0.72

Polyphen

0.25

Vest4

0.32

MutPred

0.14

Gain of solvent accessibility (P = 0.0584)

MVP

0.64

MPC

0.50

ClinPred

0.46

GERP RS

5.3

Varity_R

0.13

gMVP

0.71

Mutation Taster

=66/34

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