Variant chr10-30845081-C-G 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_001143768.2(ZNF438):c.2367G>C(p.Glu789Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,614,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ZNF438
NM_001143768.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.204

Variant links:

Genes affected

ZNF438 (HGNC:21029): (zinc finger protein 438) Enables DNA-binding transcription factor activity. Involved in negative regulation of transcription, DNA-templated. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF438 links:

ZNF438 (HGNC:):

ZNF438 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=0.011967987).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF438	NM_001143768.2 linkuse as main transcript	c.2367G>C	p.Glu789Asp	missense_variant	7/7	ENST00000436087.7	NP_001137240.1	Q7Z4V0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF438	ENST00000436087.7 linkuse as main transcript	c.2367G>C	p.Glu789Asp	missense_variant	7/7	5	NM_001143768.2	ENSP00000406934.2		Q7Z4V0-1

Frequencies

GnomAD3 genomes

AF:

0.000789

AC:

120

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00224

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000151

AC:

AN:

251492

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000106

AC:

155

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000990

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00287

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000629

Gnomad4 OTH exome

AF:

0.000629

GnomAD4 genome

AF:

0.000781

AC:

119

AN:

152272

Hom.:

Cov.:

AF XY:

0.000833

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00221

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.000994

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000198

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Dec 08, 2023

The c.2367G>C (p.E789D) alteration is located in exon 8 (coding exon 3) of the ZNF438 gene. This alteration results from a G to C substitution at nucleotide position 2367, causing the glutamic acid (E) at amino acid position 789 to be replaced by an aspartic acid (D). 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

0.17

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

.;T;T;T;.;T;.;.

Eigen

Benign

-0.037

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.82

.;.;.;.;T;T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.012

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.3

.;M;M;M;.;M;.;.

MutationTaster

Benign

0.74

D;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.8

N;N;N;N;N;N;N;N

REVEL

Benign

0.11

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.032

D;D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;D;D;.;.

Vest4

0.32

MutPred

0.33

.;Gain of ubiquitination at K788 (P = 0.1062);Gain of ubiquitination at K788 (P = 0.1062);Gain of ubiquitination at K788 (P = 0.1062);.;Gain of ubiquitination at K788 (P = 0.1062);.;.;

MVP

0.49

MPC

0.39

ClinPred

0.11

GERP RS

-0.69

Varity_R

0.10

gMVP

0.29

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