chr22-31327218-C-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014323.3(PATZ1):c.1737G>T(p.Lys579Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
PATZ1
NM_014323.3 missense
NM_014323.3 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 0.0630
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PATZ1 | NM_014323.3 | c.1737G>T | p.Lys579Asn | missense_variant | 5/5 | ENST00000266269.10 | |
PATZ1 | NM_032050.2 | c.1599G>T | p.Lys533Asn | missense_variant | 4/4 | ||
PATZ1 | NM_032052.2 | c.*58G>T | 3_prime_UTR_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PATZ1 | ENST00000266269.10 | c.1737G>T | p.Lys579Asn | missense_variant | 5/5 | 1 | NM_014323.3 | P1 | |
PATZ1 | ENST00000351933.8 | c.1599G>T | p.Lys533Asn | missense_variant | 4/4 | 1 | |||
PATZ1 | ENST00000405309.7 | c.*58G>T | 3_prime_UTR_variant | 5/5 | 1 | ||||
PIK3IP1-DT | ENST00000440456.5 | n.201-10450C>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 16, 2022 | The c.1737G>T (p.K579N) alteration is located in exon 5 (coding exon 5) of the PATZ1 gene. This alteration results from a G to T substitution at nucleotide position 1737, causing the lysine (K) at amino acid position 579 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
D;T
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Loss of methylation at K579 (P = 0.004);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.