Variant chr22-31344594-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014323.3(PATZ1):c.1009C>T(p.Pro337Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,802 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: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PATZ1
NM_014323.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.28

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16491693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PATZ1	NM_014323.3 linkuse as main transcript	c.1009C>T	p.Pro337Ser	missense_variant	1/5	ENST00000266269.10
PATZ1	NM_032050.2 linkuse as main transcript	c.1009C>T	p.Pro337Ser	missense_variant	1/4
PATZ1	NM_032051.2 linkuse as main transcript	c.1009C>T	p.Pro337Ser	missense_variant	1/3
PATZ1	NM_032052.2 linkuse as main transcript	c.1009C>T	p.Pro337Ser	missense_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PATZ1	ENST00000266269.10 linkuse as main transcript	c.1009C>T	p.Pro337Ser	missense_variant	1/5	1	NM_014323.3	P1	Q9HBE1-1
PATZ1	ENST00000351933.8 linkuse as main transcript	c.1009C>T	p.Pro337Ser	missense_variant	1/4	1			Q9HBE1-3
PATZ1	ENST00000215919.3 linkuse as main transcript	c.1009C>T	p.Pro337Ser	missense_variant	1/3	1			Q9HBE1-4
PATZ1	ENST00000405309.7 linkuse as main transcript	c.1009C>T	p.Pro337Ser	missense_variant	1/5	1			Q9HBE1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461802

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2024

The c.1009C>T (p.P337S) alteration is located in exon 1 (coding exon 1) of the PATZ1 gene. This alteration results from a C to T substitution at nucleotide position 1009, causing the proline (P) at amino acid position 337 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.056

T;.;.;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.049

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.0084

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.2

L;L;L;L

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.1

N;N;N;D

REVEL

Benign

0.084

Sift

Benign

0.29

T;T;T;T

Sift4G

Benign

0.47

T;T;T;T

Polyphen

0.52

P;B;B;B

Vest4

0.28

MutPred

0.17

Gain of phosphorylation at P337 (P = 0.0219);Gain of phosphorylation at P337 (P = 0.0219);Gain of phosphorylation at P337 (P = 0.0219);Gain of phosphorylation at P337 (P = 0.0219);

MVP

0.41

MPC

1.9

ClinPred

0.83

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.091

gMVP

0.28

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over