Variant 20-63733340-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_181485.3(ZGPAT):c.706G>A(p.Ala236Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ZGPAT
NM_181485.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.10

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.94

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZGPAT	NM_181485.3 linkuse as main transcript	c.706G>A	p.Ala236Thr	missense_variant	3/7	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.706G>A	p.Ala236Thr	missense_variant	3/7	1	NM_181485.3	ENSP00000348242.6		Q8N5A5-2
ENSG00000273154	ENST00000632538.1 linkuse as main transcript	c.121G>A	p.Ala41Thr	missense_variant	1/6	3		ENSP00000488802.1		A0A0J9YYD9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1459334

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726044

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:

0.00000360

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

Oct 03, 2024

The c.706G>A (p.A236T) alteration is located in exon 3 (coding exon 2) of the ZGPAT gene. This alteration results from a G to A substitution at nucleotide position 706, causing the alanine (A) at amino acid position 236 to be replaced by a threonine (T). 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

Pathogenic

0.81

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

.;.;.;.;T

Eigen

Uncertain

0.33

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

.;.;D;D;D

M_CAP

Pathogenic

0.62

MetaRNN

Pathogenic

0.94

D;D;D;D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Uncertain

2.6

M;M;M;M;M

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.5

N;N;N;N;N

REVEL

Pathogenic

0.69

Sift

Benign

0.050

D;D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D;D

Polyphen

0.90

P;P;D;P;D

Vest4

0.93

MutPred

0.68

Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);

MVP

0.82

MPC

0.86

ClinPred

0.97

GERP RS

4.6

Varity_R

0.42

gMVP

0.76

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