rs140074

chr22-31329648-C-Gchr22-31329648-C-T

Variant summary

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

The NM_014323.3(PATZ1):c.1508-724G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,998 control chromosomes in the GnomAD database, including 23,736 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 0.55 (23736 hom., cov: 32)
• Consequence: PATZ1 NM_014323.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492

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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATZ1	NM_014323.3	c.1508-724G>C		intron_variant		ENST00000266269.10
PATZ1	NM_032050.2	c.1508-2339G>C		intron_variant
PATZ1	NM_032052.2	c.1508-789G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PATZ1	ENST00000266269.10	c.1508-724G>C		intron_variant		1	NM_014323.3	P1
PATZ1	ENST00000351933.8	c.1508-2339G>C		intron_variant		1
PATZ1	ENST00000405309.7	c.1508-789G>C		intron_variant		1
PIK3IP1-DT	ENST00000440456.5	n.201-8020C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83427 AN: 151880 Hom.: 23700 Cov.: 32

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.549 AC: 83518 AN: 151998 Hom.: 23736 Cov.: 32 AF XY: 0.558 AC XY: 41466 AN XY: 74294

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.941

Gnomad4 SAS AF: 0.610

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.519

Alfa AF: 0.404 Hom.: 1114

Bravo AF: 0.554

Asia WGS AF: 0.772 AC: 2686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	1.5
Dann	Benign	0.80

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: rs140074; hg19: chr22-31725634;