rs714909

Variant names:

• chr22-31345081-G-A
• rs714909
• NM_014323.3:c.522C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014323.3(PATZ1):​c.522C>T​(p.Leu174Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,614,008 control chromosomes in the GnomAD database, including 60,480 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (4336 hom., cov: 33)
  • Exomes 𝑓: 0.27 (56144 hom.)
• Consequence: PATZ1 NM_014323.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480
• Publications: 24 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=-0.48 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PATZ1	NM_014323.3	c.522C>T	p.Leu174Leu	synonymous_variant	Exon 1 of 5	ENST00000266269.10	NP_055138.2
PATZ1	NM_032050.2	c.522C>T	p.Leu174Leu	synonymous_variant	Exon 1 of 4		NP_114439.1
PATZ1	NM_032051.2	c.522C>T	p.Leu174Leu	synonymous_variant	Exon 1 of 3		NP_114440.1
PATZ1	NM_032052.2	c.522C>T	p.Leu174Leu	synonymous_variant	Exon 1 of 5		NP_114441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PATZ1	ENST00000266269.10	c.522C>T	p.Leu174Leu	synonymous_variant	Exon 1 of 5	1	NM_014323.3	ENSP00000266269.5
PATZ1	ENST00000351933.8	c.522C>T	p.Leu174Leu	synonymous_variant	Exon 1 of 4	1		ENSP00000337520.4
PATZ1	ENST00000215919.3	c.522C>T	p.Leu174Leu	synonymous_variant	Exon 1 of 3	1		ENSP00000215919.3
PATZ1	ENST00000405309.7	c.522C>T	p.Leu174Leu	synonymous_variant	Exon 1 of 5	1		ENSP00000384173.3

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31983 AN: 152102 Hom.: 4332 Cov.: 33

Gnomad AFR AF: 0.0528

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.194

GnomAD2 exomes AF: 0.246 AC: 61691 AN: 251174 AF XY: 0.247

Gnomad AFR exome AF: 0.0460

Gnomad AMR exome AF: 0.270

Gnomad ASJ exome AF: 0.180

Gnomad EAS exome AF: 0.138

Gnomad FIN exome AF: 0.341

Gnomad NFE exome AF: 0.280

Gnomad OTH exome AF: 0.239

GnomAD4 exome AF: 0.271 AC: 395710 AN: 1461788 Hom.: 56144 Cov.: 37 AF XY: 0.268 AC XY: 195225 AN XY: 727208

African (AFR) AF: 0.0423 AC: 1417 AN: 33480

American (AMR) AF: 0.269 AC: 12014 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 4777 AN: 26134

East Asian (EAS) AF: 0.116 AC: 4614 AN: 39700

South Asian (SAS) AF: 0.218 AC: 18800 AN: 86256

European-Finnish (FIN) AF: 0.343 AC: 18329 AN: 53386

Middle Eastern (MID) AF: 0.169 AC: 972 AN: 5768

European-Non Finnish (NFE) AF: 0.288 AC: 320050 AN: 1111946

Other (OTH) AF: 0.244 AC: 14737 AN: 60394

GnomAD4 genome AF: 0.210 AC: 31993 AN: 152220 Hom.: 4336 Cov.: 33 AF XY: 0.213 AC XY: 15816 AN XY: 74412

African (AFR) AF: 0.0526 AC: 2186 AN: 41568

American (AMR) AF: 0.237 AC: 3622 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 670 AN: 3472

East Asian (EAS) AF: 0.122 AC: 631 AN: 5184

South Asian (SAS) AF: 0.213 AC: 1024 AN: 4818

European-Finnish (FIN) AF: 0.343 AC: 3630 AN: 10586

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19517 AN: 67976

Other (OTH) AF: 0.192 AC: 406 AN: 2112

Alfa AF: 0.245 Hom.: 4315

Bravo AF: 0.195

Asia WGS AF: 0.142 AC: 494 AN: 3478

EpiCase AF: 0.260

EpiControl AF: 0.254

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.6
DANN	Benign	0.94
PhyloP100		-0.48
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs714909; hg19: chr22-31741067; COSMIC: COSV53228637; COSMIC: COSV53228637;