1-151404931-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015100.4(POGZ):c.4104T>G(p.Thr1368Thr) 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 (★★). Synonymous variant affecting the same amino acid position (i.e. T1368T) has been classified as Likely 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

Publications

16 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: Labcorp Genetics (formerly Invitae), Illumina, G2P, Orphanet, ClinGen

POGZ links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
POGZ	NM_015100.4 link	c.4104T>G	p.Thr1368Thr	synonymous_variant	Exon 19 of 19	ENST00000271715.7	NP_055915.2	Q7Z3K3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POGZ	ENST00000271715.7 link	c.4104T>G	p.Thr1368Thr	synonymous_variant	Exon 19 of 19	1	NM_015100.4	ENSP00000271715.2		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

GnomAD2 exomes

AF:

0.114

AC:

28715

AN:

251466

AF XY:

0.0999

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 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

African (AFR)

AF:

0.269

AC:

9006

AN:

33480

American (AMR)

AF:

0.316

AC:

14143

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00945

AC:

247

AN:

26136

East Asian (EAS)

AF:

0.456

AC:

18100

AN:

39700

South Asian (SAS)

AF:

0.0895

AC:

7718

AN:

86258

European-Finnish (FIN)

AF:

0.0647

AC:

3457

AN:

53420

Middle Eastern (MID)

AF:

0.0270

AC:

156

AN:

5768

European-Non Finnish (NFE)

AF:

0.00255

AC:

2840

AN:

1112008

Other (OTH)

AF:

0.0670

AC:

4047

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

2720

5440

8160

10880

13600

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.118

AC:

17989

AN:

152154

Hom.:

2360

Cov.:

AF XY:

0.125

AC XY:

9272

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.251

AC:

10427

AN:

41468

American (AMR)

AF:

0.224

AC:

3419

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00692

AC:

AN:

3470

East Asian (EAS)

AF:

0.442

AC:

2284

AN:

5162

South Asian (SAS)

AF:

0.111

AC:

535

AN:

4824

European-Finnish (FIN)

AF:

0.0759

AC:

805

AN:

10604

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00415

AC:

282

AN:

68022

Other (OTH)

AF:

0.0960

AC:

203

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

674

1347

2021

2694

3368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0432

Hom.:

1262

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 03, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Mar 24, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.1

(source)

DANN

Benign

0.59

PhyloP100

-0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=100/0

polymorphism (auto)

(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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1-151404931-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over