chr22-31327218-C-A

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

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0630
Variant links:
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)

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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
PATZ1NM_014323.3 linkuse as main transcriptc.1737G>T p.Lys579Asn missense_variant 5/5 ENST00000266269.10
PATZ1NM_032050.2 linkuse as main transcriptc.1599G>T p.Lys533Asn missense_variant 4/4
PATZ1NM_032052.2 linkuse as main transcriptc.*58G>T 3_prime_UTR_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PATZ1ENST00000266269.10 linkuse as main transcriptc.1737G>T p.Lys579Asn missense_variant 5/51 NM_014323.3 P1Q9HBE1-1
PATZ1ENST00000351933.8 linkuse as main transcriptc.1599G>T p.Lys533Asn missense_variant 4/41 Q9HBE1-3
PATZ1ENST00000405309.7 linkuse as main transcriptc.*58G>T 3_prime_UTR_variant 5/51 Q9HBE1-2
PIK3IP1-DTENST00000440456.5 linkuse as main transcriptn.201-10450C>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
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 submitterclinical testingAmbry GeneticsMar 16, 2022The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T;.
Eigen
Benign
0.13
Eigen_PC
Benign
0.080
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.036
D
MetaRNN
Uncertain
0.54
D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-1.5
N;N
REVEL
Benign
0.17
Sift
Benign
0.038
D;T
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
D;D
Vest4
0.68
MutPred
0.39
Loss of methylation at K579 (P = 0.004);.;
MVP
0.65
MPC
2.2
ClinPred
0.88
D
GERP RS
-0.60
Varity_R
0.083
gMVP
0.53

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-31723204; API