Variant 1-151404931-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015100.4(POGZ):c.4104T>G(p.Thr1368=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0481 in 1,614,044 control chromosomes in the GnomAD database, including 11,357 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 2360 hom., cov: 32)

Exomes 𝑓: 0.041 ( 8997 hom. )

Consequence

POGZ
NM_015100.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.515

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-151404931-A-C is Benign according to our data. Variant chr1-151404931-A-C is described in ClinVar as [Benign]. Clinvar id is 587824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.515 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POGZ	NM_015100.4 linkuse as main transcript	c.4104T>G	p.Thr1368=	synonymous_variant	19/19	ENST00000271715.7	NP_055915.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POGZ	ENST00000271715.7 linkuse as main transcript	c.4104T>G	p.Thr1368=	synonymous_variant	19/19	1	NM_015100.4	ENSP00000271715	P3	Q7Z3K3-1

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17942

AN:

152036

Hom.:

2351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.443

Gnomad SAS

AF:

0.111

Gnomad FIN

AF:

0.0759

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00413

Gnomad OTH

AF:

0.0932

GnomAD3 exomes

AF:

0.114

AC:

28715

AN:

251466

Hom.:

4469

AF XY:

0.0999

AC XY:

13577

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.259

Gnomad AMR exome

AF:

0.330

Gnomad ASJ exome

AF:

0.0105

Gnomad EAS exome

AF:

0.411

Gnomad SAS exome

AF:

0.0930

Gnomad FIN exome

AF:

0.0698

Gnomad NFE exome

AF:

0.00485

Gnomad OTH exome

AF:

0.0789

GnomAD4 exome

AF:

0.0408

AC:

59714

AN:

1461890

Hom.:

8997

Cov.:

AF XY:

0.0402

AC XY:

29258

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.269

Gnomad4 AMR exome

AF:

0.316

Gnomad4 ASJ exome

AF:

0.00945

Gnomad4 EAS exome

AF:

0.456

Gnomad4 SAS exome

AF:

0.0895

Gnomad4 FIN exome

AF:

0.0647

Gnomad4 NFE exome

AF:

0.00255

Gnomad4 OTH exome

AF:

0.0670

GnomAD4 genome

AF:

0.118

AC:

17989

AN:

152154

Hom.:

2360

Cov.:

AF XY:

0.125

AC XY:

9272

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.251

Gnomad4 AMR

AF:

0.224

Gnomad4 ASJ

AF:

0.00692

Gnomad4 EAS

AF:

0.442

Gnomad4 SAS

AF:

0.111

Gnomad4 FIN

AF:

0.0759

Gnomad4 NFE

AF:

0.00415

Gnomad4 OTH

AF:

0.0960

Alfa

AF:

0.0315

Hom.:

741

Bravo

AF:

0.137

Asia WGS

AF:

0.282

AC:

979

AN:

3478

EpiCase

AF:

0.00393

EpiControl

AF:

0.00439

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 03, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 24, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.1

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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