Variant chr1-151411656-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015100.4(POGZ):c.1895A>G(p.Asn632Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,612,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N632I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

POGZ
NM_015100.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.14

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.061409175).

BP6

Variant 1-151411656-T-C is Benign according to our data. Variant chr1-151411656-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 446070.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000132 (20/151860) while in subpopulation AFR AF= 0.000169 (7/41388). AF 95% confidence interval is 0.0000791. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POGZ	NM_015100.4 link	c.1895A>G	p.Asn632Ser	missense_variant	12/19	ENST00000271715.7	NP_055915.2	Q7Z3K3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POGZ	ENST00000271715.7 link	c.1895A>G	p.Asn632Ser	missense_variant	12/19	1	NM_015100.4	ENSP00000271715.2		Q7Z3K3-1

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

151790

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000191

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000207

AC:

AN:

250702

Hom.:

AF XY:

0.000229

AC XY:

AN XY:

135546

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000291

Gnomad OTH exome

AF:

0.000819

GnomAD4 exome

AF:

0.000239

AC:

349

AN:

1461076

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

176

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000581

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.000274

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000132

AC:

AN:

151860

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000191

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.000477

Alfa

AF:

0.000118

Hom.:

Bravo

AF:

0.000159

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000247

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Aug 31, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.022

.;T;.;.;.;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.89

D;D;D;D;D;D

M_CAP

Benign

0.0098

MetaRNN

Benign

0.061

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.39

.;N;.;.;.;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.21

N;N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.15

T;T;T;T;T;T

Sift4G

Benign

0.34

T;T;T;T;T;T

Polyphen

0.97

D;P;D;.;.;B

Vest4

0.14

MVP

0.70

MPC

0.58

ClinPred

0.035

GERP RS

3.8

Varity_R

0.027

gMVP

0.18

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