chr22-31342438-A-G

Variant names:

• chr22-31342438-A-G
• rs2240427
• NM_014323.3:c.1335+459T>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.1335+459T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0581 in 152,104 control chromosomes in the GnomAD database, including 642 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 0.058 (642 hom., cov: 32)
• Consequence: PATZ1 NM_014323.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PATZ1	NM_014323.3	c.1335+459T>C		intron_variant	Intron 2 of 4	ENST00000266269.10	NP_055138.2
PATZ1	NM_032050.2	c.1335+459T>C		intron_variant	Intron 2 of 3		NP_114439.1
PATZ1	NM_032051.2	c.1335+459T>C		intron_variant	Intron 2 of 2		NP_114440.1
PATZ1	NM_032052.2	c.1335+459T>C		intron_variant	Intron 2 of 4		NP_114441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PATZ1	ENST00000266269.10	c.1335+459T>C		intron_variant	Intron 2 of 4	1	NM_014323.3	ENSP00000266269.5

Frequencies

GnomAD3 genomes AF: 0.0580 AC: 8813 AN: 151986 Hom.: 634 Cov.: 32

Gnomad AFR AF: 0.0708

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.0626

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0221

Gnomad OTH AF: 0.0617

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

GnomAD4 genome AF: 0.0581 AC: 8841 AN: 152104 Hom.: 642 Cov.: 32 AF XY: 0.0618 AC XY: 4598 AN XY: 74368

African (AFR) AF: 0.0713 AC: 2958 AN: 41476

American (AMR) AF: 0.113 AC: 1723 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3472

East Asian (EAS) AF: 0.377 AC: 1938 AN: 5140

South Asian (SAS) AF: 0.0623 AC: 300 AN: 4818

European-Finnish (FIN) AF: 0.0105 AC: 111 AN: 10612

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.0221 AC: 1503 AN: 67992

Other (OTH) AF: 0.0611 AC: 129 AN: 2112

Alfa AF: 0.0237 Hom.: 32

Bravo AF: 0.0695

Asia WGS AF: 0.190 AC: 659 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.8
DANN	Benign	0.85
PhyloP100		0.096
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: rs2240427; hg19: chr22-31738424;