Variant 20-63708590-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181485.3(ZGPAT):c.10G>A(p.Glu4Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000278 in 1,599,396 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

ZGPAT
NM_181485.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.70

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.056249917).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZGPAT	NM_181485.3 linkuse as main transcript	c.10G>A	p.Glu4Lys	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.10G>A	p.Glu4Lys	missense_variant	2/7	1	NM_181485.3	ENSP00000348242.6		Q8N5A5-2

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000254

AC:

AN:

239816

Hom.:

AF XY:

0.000296

AC XY:

AN XY:

131540

show subpopulations

Gnomad AFR exome

AF:

0.000136

Gnomad AMR exome

AF:

0.0000892

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000366

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000402

Gnomad OTH exome

AF:

0.000342

GnomAD4 exome

AF:

0.000270

AC:

391

AN:

1447054

Hom.:

Cov.:

AF XY:

0.000291

AC XY:

209

AN XY:

717502

show subpopulations

Gnomad4 AFR exome

AF:

0.0000905

Gnomad4 AMR exome

AF:

0.000206

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000619

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000265

Gnomad4 OTH exome

AF:

0.000369

GnomAD4 genome

AF:

0.000354

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000461

Hom.:

Bravo

AF:

0.000427

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000234

AC:

ExAC

AF:

0.000290

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Sep 01, 2021

The c.10G>A (p.E4K) 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 10, causing the glutamic acid (E) at amino acid position 4 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

0.10

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.034

.;.;.;T;.;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.89

.;.;D;D;D;D

M_CAP

Benign

0.044

MetaRNN

Benign

0.056

T;T;T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.8

L;L;L;.;L;L

MutationTaster

Benign

0.65

N;N;N;N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.6

N;N;N;N;N;N

REVEL

Benign

0.042

Sift

Benign

0.23

T;T;T;D;T;T

Sift4G

Benign

0.066

T;T;T;D;T;T

Polyphen

0.51

P;P;P;.;P;P

Vest4

0.35

MVP

0.055

MPC

0.41

ClinPred

0.035

GERP RS

3.0

Varity_R

0.15

gMVP

0.12

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