rs140074

Variant names:

• chr22-31329648-C-G
• rs140074
• NM_014323.3:c.1508-724G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-31329648-C-G
• chr22-31329648-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014323.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PATZ1	NM_014323.3	MANE Select	c.1508-724G>C		intron	N/A	NP_055138.2
	PATZ1	NM_032050.2		c.1508-2339G>C		intron	N/A	NP_114439.1
	PATZ1	NM_032052.2		c.1508-789G>C		intron	N/A	NP_114441.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PATZ1	ENST00000266269.10	TSL:1 MANE Select	c.1508-724G>C		intron	N/A	ENSP00000266269.5
	PATZ1	ENST00000351933.8	TSL:1	c.1508-2339G>C		intron	N/A	ENSP00000337520.4
	PATZ1	ENST00000405309.7	TSL:1	c.1508-789G>C		intron	N/A	ENSP00000384173.3

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

African (AFR) AF: 0.563 AC: 23331 AN: 41432

American (AMR) AF: 0.630 AC: 9622 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1372 AN: 3472

East Asian (EAS) AF: 0.941 AC: 4865 AN: 5172

South Asian (SAS) AF: 0.610 AC: 2936 AN: 4812

European-Finnish (FIN) AF: 0.573 AC: 6045 AN: 10558

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33708 AN: 67960

Other (OTH) AF: 0.519 AC: 1097 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.5
DANN	Benign	0.80
PhyloP100		-0.49
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: rs140074; hg19: chr22-31725634;