20-63709014-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_181485.3(ZGPAT):​c.434T>A​(p.Leu145Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ZGPAT
NM_181485.3 missense

Scores

6
9
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.88
Variant links:
Genes affected
ZGPAT (HGNC:15948): (zinc finger CCCH-type and G-patch domain containing) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of epidermal growth factor-activated receptor activity and negative regulation of transcription by RNA polymerase II. Located in nucleoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.819

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZGPATNM_181485.3 linkuse as main transcriptc.434T>A p.Leu145Gln missense_variant 2/7 ENST00000355969.11 NP_852150.2 Q8N5A5-2A0A0S2Z5X3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZGPATENST00000355969.11 linkuse as main transcriptc.434T>A p.Leu145Gln missense_variant 2/71 NM_181485.3 ENSP00000348242.6 Q8N5A5-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
35
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 GeneticsOct 13, 2023The c.434T>A (p.L145Q) alteration is located in exon 2 (coding exon 1) of the ZGPAT gene. This alteration results from a T to A substitution at nucleotide position 434, causing the leucine (L) at amino acid position 145 to be replaced by a glutamine (Q). 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
0.50
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
.;.;.;.;T
Eigen
Pathogenic
0.70
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
.;.;D;D;D
M_CAP
Benign
0.053
D
MetaRNN
Pathogenic
0.82
D;D;D;D;D
MetaSVM
Benign
-0.81
T
MutationAssessor
Pathogenic
3.0
M;M;M;M;M
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-3.5
D;D;D;D;D
REVEL
Uncertain
0.39
Sift
Uncertain
0.0030
D;D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D;D
Polyphen
1.0
D;D;D;D;D
Vest4
0.93
MutPred
0.38
Gain of catalytic residue at L145 (P = 0.0102);Gain of catalytic residue at L145 (P = 0.0102);Gain of catalytic residue at L145 (P = 0.0102);Gain of catalytic residue at L145 (P = 0.0102);Gain of catalytic residue at L145 (P = 0.0102);
MVP
0.39
MPC
0.94
ClinPred
1.0
D
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.90
gMVP
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr20-62340366; API