NM_014323.3:c.1507+1633T>C

Variant names:

• chr22-31334059-A-G
• rs2057951
• NM_014323.3:c.1507+1633T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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]

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PATZ1	NM_014323.3	c.1507+1633T>C		intron_variant	Intron 3 of 4	ENST00000266269.10	NP_055138.2
PATZ1	NM_032050.2	c.1507+1633T>C		intron_variant	Intron 3 of 3		NP_114439.1
PATZ1	NM_032052.2	c.1507+1633T>C		intron_variant	Intron 3 of 4		NP_114441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PATZ1	ENST00000266269.10	c.1507+1633T>C		intron_variant	Intron 3 of 4	1	NM_014323.3	ENSP00000266269.5

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

African (AFR) AF: 0.570 AC: 23609 AN: 41444

American (AMR) AF: 0.342 AC: 5232 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 508 AN: 3468

East Asian (EAS) AF: 0.390 AC: 2014 AN: 5160

South Asian (SAS) AF: 0.180 AC: 867 AN: 4830

European-Finnish (FIN) AF: 0.143 AC: 1517 AN: 10592

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9497 AN: 67984

Other (OTH) AF: 0.264 AC: 559 AN: 2114

Alfa AF: 0.235 Hom.: 1076

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
PhyloP100		-0.26
Mutation Taster		=100/0	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: rs2057951; hg19: chr22-31730045;