22-31326900-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014323.3(PATZ1):c.2055A>C(p.Glu685Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 1,611,804 control chromosomes in the GnomAD database, including 4,706 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.044 ( 544 hom., cov: 32)

Exomes 𝑓: 0.022 ( 4162 hom. )

Consequence

PATZ1
NM_014323.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.74

Publications

20 publications found

Variant links:

Genes affected

PATZ1 (HGNC:13071): (POZ/BTB and AT hook containing zinc finger 1) The protein encoded by this gene contains an A-T hook DNA binding motif which usually binds to other DNA binding structures to play an important role in chromatin modeling and transcription regulation. Its Poz domain is thought to function as a site for protein-protein interaction and is required for transcriptional repression, and the zinc-fingers comprise the DNA binding domain. Since the encoded protein has typical features of a transcription factor, it is postulated to be a repressor of gene expression. In small round cell sarcoma, this gene is fused to EWS by a small inversion of 22q, then the hybrid is thought to be translocated (t(1;22)(p36.1;q12). The rearrangement of chromosome 22 involves intron 8 of EWS and exon 1 of this gene creating a chimeric sequence containing the transactivation domain of EWS fused to zinc finger domain of this protein. This is a distinct example of an intra-chromosomal rearrangement of chromosome 22. Four alternatively spliced transcript variants are described for this gene. [provided by RefSeq, Jul 2008]

PATZ1 links:

PIK3IP1-DT (HGNC:41072): (PIK3IP1 divergent transcript)

PIK3IP1-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002393514).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PATZ1	NM_014323.3 link	c.2055A>C	p.Glu685Asp	missense_variant	Exon 5 of 5	ENST00000266269.10	NP_055138.2	Q9HBE1-1A0A024R1M5
PATZ1	NM_032050.2 link	c.1917A>C	p.Glu639Asp	missense_variant	Exon 4 of 4		NP_114439.1	Q9HBE1-3A0A024R1F8
PATZ1	NM_032052.2 link	c.*376A>C		3_prime_UTR_variant	Exon 5 of 5		NP_114441.1	Q9HBE1-2A0A024R1H7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PATZ1	ENST00000266269.10 link	c.2055A>C	p.Glu685Asp	missense_variant	Exon 5 of 5	1	NM_014323.3	ENSP00000266269.5		Q9HBE1-1

Frequencies

GnomAD3 genomes

AF:

0.0439

AC:

6675

AN:

152114

Hom.:

536

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0665

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0971

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.0392

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00238

Gnomad OTH

AF:

0.0435

GnomAD2 exomes

AF:

0.0586

AC:

14645

AN:

250050

AF XY:

0.0508

show subpopulations

Gnomad AFR exome

AF:

0.0700

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.0169

Gnomad EAS exome

AF:

0.363

Gnomad FIN exome

AF:

0.00334

Gnomad NFE exome

AF:

0.00255

Gnomad OTH exome

AF:

0.0350

GnomAD4 exome

AF:

0.0225

AC:

32775

AN:

1459570

Hom.:

4162

Cov.:

AF XY:

0.0218

AC XY:

15815

AN XY:

725902

show subpopulations

African (AFR)

AF:

0.0700

AC:

2337

AN:

33364

American (AMR)

AF:

0.143

AC:

6358

AN:

44402

Ashkenazi Jewish (ASJ)

AF:

0.0197

AC:

514

AN:

26044

East Asian (EAS)

AF:

0.403

AC:

15996

AN:

39652

South Asian (SAS)

AF:

0.0305

AC:

2623

AN:

86050

European-Finnish (FIN)

AF:

0.00352

AC:

188

AN:

53374

Middle Eastern (MID)

AF:

0.0264

AC:

152

AN:

5752

European-Non Finnish (NFE)

AF:

0.00224

AC:

2493

AN:

1110636

Other (OTH)

AF:

0.0351

AC:

2114

AN:

60296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1383

2767

4150

5534

6917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.0440

AC:

6699

AN:

152234

Hom.:

544

Cov.:

AF XY:

0.0476

AC XY:

3547

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0670

AC:

2783

AN:

41532

American (AMR)

AF:

0.0970

AC:

1484

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0182

AC:

AN:

3470

East Asian (EAS)

AF:

0.366

AC:

1890

AN:

5162

South Asian (SAS)

AF:

0.0384

AC:

185

AN:

4820

European-Finnish (FIN)

AF:

0.00311

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00238

AC:

162

AN:

68012

Other (OTH)

AF:

0.0431

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

286

572

857

1143

1429

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.0240

Hom.:

969

Bravo

AF:

0.0544

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.0631

AC:

278

ESP6500EA

AF:

0.00267

AC:

ExAC

AF:

0.0542

AC:

6579

Asia WGS

AF:

0.175

AC:

609

AN:

3478

EpiCase

AF:

0.00387

EpiControl

AF:

0.00385

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.78

T;T

MetaRNN

Benign

0.0024

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.55

N;.

PhyloP100

1.7

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.71

N;N

REVEL

Benign

0.11

Sift

Uncertain

0.019

D;D

Sift4G

Benign

0.12

T;T

Polyphen

0.82

P;P

Vest4

0.077

MutPred

0.11

Loss of methylation at K687 (P = 0.06);.;

MPC

2.0

ClinPred

0.019

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.094

gMVP

0.089

Mutation Taster

=96/4

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over