rs2057951

chr22-31334059-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014323.3(PATZ1):c.1507+1633T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,076 control chromosomes in the GnomAD database, including 9,014 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 0.29 (9014 hom., cov: 32)
• Consequence: PATZ1 NM_014323.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

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]

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATZ1	NM_014323.3	c.1507+1633T>C		intron_variant		ENST00000266269.10
PATZ1	NM_032050.2	c.1507+1633T>C		intron_variant
PATZ1	NM_032052.2	c.1507+1633T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PATZ1	ENST00000266269.10	c.1507+1633T>C		intron_variant		1	NM_014323.3	P1
PATZ1	ENST00000351933.8	c.1507+1633T>C		intron_variant		1
PATZ1	ENST00000405309.7	c.1507+1633T>C		intron_variant		1
PIK3IP1-DT	ENST00000440456.5	n.201-3609A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43874 AN: 151956 Hom.: 8979 Cov.: 32

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.267

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.289 AC: 43953 AN: 152076 Hom.: 9014 Cov.: 32 AF XY: 0.291 AC XY: 21638 AN XY: 74354

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.342

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.264

Alfa AF: 0.223 Hom.: 941

Bravo AF: 0.317

Asia WGS AF: 0.292 AC: 1018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.9
Dann	Benign	0.29

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

LitVar

Other links and lift over

dbSNP: rs2057951; hg19: chr22-31730045;