Variant 22-31344680-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014323.3(PATZ1):c.923G>T(p.Arg308Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,594 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PATZ1
NM_014323.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.68

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PATZ1	NM_014323.3 linkuse as main transcript	c.923G>T	p.Arg308Leu	missense_variant	1/5	ENST00000266269.10
PATZ1	NM_032050.2 linkuse as main transcript	c.923G>T	p.Arg308Leu	missense_variant	1/4
PATZ1	NM_032051.2 linkuse as main transcript	c.923G>T	p.Arg308Leu	missense_variant	1/3
PATZ1	NM_032052.2 linkuse as main transcript	c.923G>T	p.Arg308Leu	missense_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PATZ1	ENST00000266269.10 linkuse as main transcript	c.923G>T	p.Arg308Leu	missense_variant	1/5	1	NM_014323.3	P1	Q9HBE1-1
PATZ1	ENST00000351933.8 linkuse as main transcript	c.923G>T	p.Arg308Leu	missense_variant	1/4	1			Q9HBE1-3
PATZ1	ENST00000215919.3 linkuse as main transcript	c.923G>T	p.Arg308Leu	missense_variant	1/3	1			Q9HBE1-4
PATZ1	ENST00000405309.7 linkuse as main transcript	c.923G>T	p.Arg308Leu	missense_variant	1/5	1			Q9HBE1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461594

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727080

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

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

Nov 18, 2022

The c.923G>T (p.R308L) alteration is located in exon 1 (coding exon 1) of the PATZ1 gene. This alteration results from a G to T substitution at nucleotide position 923, causing the arginine (R) at amino acid position 308 to be replaced by a leucine (L). 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

Uncertain

0.54

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

T;.;.;.

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.90

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.59

D;D;D;D

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.34

N;N;N;N

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-4.6

D;D;D;D

REVEL

Uncertain

0.41

Sift

Benign

0.089

T;D;D;D

Sift4G

Benign

0.063

T;D;T;D

Polyphen

0.99

D;D;D;D

Vest4

0.51

MutPred

0.32

Loss of disorder (P = 0.0662);Loss of disorder (P = 0.0662);Loss of disorder (P = 0.0662);Loss of disorder (P = 0.0662);

MVP

0.68

MPC

2.3

ClinPred

1.0

GERP RS

4.8

Varity_R

0.46

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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