Variant chr20-63735222-A-G 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.1055A>G(p.Lys352Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000634 in 1,420,282 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: 34)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

ZGPAT
NM_181485.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.09

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:

ENSG00000273154 (HGNC:):

ENSG00000273154 links:

Genome browser will be placed here

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=0.25029936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZGPAT	NM_181485.3 linkuse as main transcript	c.1055A>G	p.Lys352Arg	missense_variant	6/7	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.1055A>G	p.Lys352Arg	missense_variant	6/7	1	NM_181485.3	ENSP00000348242.6		Q8N5A5-2
ENSG00000273154	ENST00000632538.1 linkuse as main transcript	c.322+1447A>G		intron_variant		3		ENSP00000488802.1		A0A0J9YYD9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000918

AC:

AN:

217884

Hom.:

AF XY:

0.0000169

AC XY:

AN XY:

118616

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000395

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000992

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000634

AC:

AN:

1420282

Hom.:

Cov.:

AF XY:

0.00000853

AC XY:

AN XY:

703264

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:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000366

Gnomad4 OTH exome

AF:

0.0000171

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

May 08, 2024

The c.1115A>G (p.K372R) alteration is located in exon 6 (coding exon 5) of the ZGPAT gene. This alteration results from a A to G substitution at nucleotide position 1115, causing the lysine (K) at amino acid position 372 to be replaced by an arginine (R). 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

0.076

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.089

.;.;.;.;T

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.75

.;.;T;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.25

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;.;.;.;L

MutationTaster

Benign

0.99

D;D;D;D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.1

N;N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.14

T;T;T;T;T

Sift4G

Benign

0.15

T;T;T;T;T

Polyphen

0.97

D;D;P;D;D

Vest4

0.28

MutPred

0.47

.;.;.;.;Loss of ubiquitination at K372 (P = 0.0167);

MVP

0.12

MPC

0.23

ClinPred

0.31

GERP RS

3.1

Varity_R

0.049

gMVP

0.40

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over