Variant 20-63708803-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181485.3(ZGPAT):c.223G>A(p.Glu75Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ZGPAT
NM_181485.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.828

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]

ZGPAT links:

ZGPAT (HGNC:):

ZGPAT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10689804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZGPAT	NM_181485.3 linkuse as main transcript	c.223G>A	p.Glu75Lys	missense_variant	2/7	ENST00000355969.11	NP_852150.2	Q8N5A5-2A0A0S2Z5X3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZGPAT	ENST00000355969.11 linkuse as main transcript	c.223G>A	p.Glu75Lys	missense_variant	2/7	1	NM_181485.3	ENSP00000348242.6		Q8N5A5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453520

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721590

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 17, 2022

The c.223G>A (p.E75K) alteration is located in exon 2 (coding exon 1) of the ZGPAT gene. This alteration results from a G to A substitution at nucleotide position 223, causing the glutamic acid (E) at amino acid position 75 to be replaced by a lysine (K). 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

Benign

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.027

.;.;.;T;.;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.49

.;.;T;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.11

T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;N;N;.;N;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-1.3

N;N;N;N;N;N

REVEL

Benign

0.058

Sift

Benign

0.40

T;T;T;D;T;T

Sift4G

Benign

0.67

T;T;T;T;T;T

Polyphen

0.17

B;B;B;.;B;B

Vest4

0.11

MutPred

0.27

Gain of ubiquitination at E75 (P = 7e-04);Gain of ubiquitination at E75 (P = 7e-04);Gain of ubiquitination at E75 (P = 7e-04);Gain of ubiquitination at E75 (P = 7e-04);Gain of ubiquitination at E75 (P = 7e-04);Gain of ubiquitination at E75 (P = 7e-04);

MVP

0.014

MPC

0.32

ClinPred

0.20

GERP RS

4.1

Varity_R

0.19

gMVP

0.21

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over