22-31328848-G-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The ENST00000405309.7(PATZ1):c.1519C>T(p.Pro507Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
PATZ1
ENST00000405309.7 missense
ENST00000405309.7 missense
Scores
1
1
13
Clinical Significance
Conservation
PhyloP100: 6.84
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.13059035).
BP6
Variant 22-31328848-G-A is Benign according to our data. Variant chr22-31328848-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3208954.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PATZ1 | NM_014323.3 | c.1584C>T | p.His528= | synonymous_variant | 4/5 | ENST00000266269.10 | |
PATZ1 | NM_032052.2 | c.1519C>T | p.Pro507Ser | missense_variant | 4/5 | ||
PATZ1 | NM_032050.2 | c.1508-1539C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PATZ1 | ENST00000405309.7 | c.1519C>T | p.Pro507Ser | missense_variant | 4/5 | 1 | |||
PATZ1 | ENST00000266269.10 | c.1584C>T | p.His528= | synonymous_variant | 4/5 | 1 | NM_014323.3 | P1 | |
PATZ1 | ENST00000351933.8 | c.1508-1539C>T | intron_variant | 1 | |||||
PIK3IP1-DT | ENST00000440456.5 | n.201-8820G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251322Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135834
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461606Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727100
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 07, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of glycosylation at P507 (P = 0.0247);
MVP
ClinPred
T
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at