rs72996036

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The NM_015100.4(POGZ):c.1850G>A(p.Arg617Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,613,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

POGZ
NM_015100.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 1.87

Publications

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

POGZ links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_015100.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.110709906).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000145 (22/151920) while in subpopulation AFR AF = 0.000411 (17/41400). AF 95% confidence interval is 0.000261. There are 0 homozygotes in GnomAd4. There are 13 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 22 AD gene.

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.1850G>A	p.Arg617Gln	missense	Exon 12 of 19	NP_055915.2
POGZ	NM_001410860.1		c.1871G>A	p.Arg624Gln	missense	Exon 12 of 19	NP_001397789.1	A0A8V8TQ67
POGZ	NM_001194937.2		c.1823G>A	p.Arg608Gln	missense	Exon 12 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.1850G>A	p.Arg617Gln	missense	Exon 12 of 19	ENSP00000271715.2	Q7Z3K3-1
POGZ	ENST00000392723.6	TSL:1	c.1691G>A	p.Arg564Gln	missense	Exon 11 of 18	ENSP00000376484.1	Q7Z3K3-2
POGZ	ENST00000368863.6	TSL:1	c.1565G>A	p.Arg522Gln	missense	Exon 10 of 17	ENSP00000357856.2	Q7Z3K3-5

Frequencies

GnomAD3 genomes

AF:

0.000152

AC:

AN:

151812

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000436

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000960

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

251376

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1461414

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727052

show subpopulations

African (AFR)

AF:

0.000329

AC:

AN:

33470

American (AMR)

AF:

0.0000224

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111608

Other (OTH)

AF:

0.0000331

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000145

AC:

AN:

151920

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.000411

AC:

AN:

41400

American (AMR)

AF:

0.000197

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10514

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67986

Other (OTH)

AF:

0.000950

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000121

Hom.:

Bravo

AF:

0.000125

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome (2)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.63

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.086

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.033

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.3

PhyloP100

1.9

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.7

REVEL

Benign

0.22

Sift

Uncertain

0.027

Sift4G

Benign

0.069

Varity_R

0.11

gMVP

0.72

Mutation Taster

=98/2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over