Variant chr10-30845098-T-C 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_001143768.2(ZNF438):c.2350A>G(p.Met784Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

ZNF438
NM_001143768.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14

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:

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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=0.17151907).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF438	NM_001143768.2 linkuse as main transcript	c.2350A>G	p.Met784Val	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.2350A>G	p.Met784Val	missense_variant	7/7	5	NM_001143768.2	ENSP00000406934.2		Q7Z4V0-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Mar 06, 2023

The c.2350A>G (p.M784V) alteration is located in exon 8 (coding exon 3) of the ZNF438 gene. This alteration results from a A to G substitution at nucleotide position 2350, causing the methionine (M) at amino acid position 784 to be replaced by a valine (V). 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

0.075

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.1

DANN

Benign

0.25

DEOGEN2

Benign

0.00088

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

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.51

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

M_CAP

Benign

0.0053

MetaRNN

Benign

0.17

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

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.34

.;N;N;N;.;N;.;.

PrimateAI

Benign

0.29

PROVEAN

Benign

0.28

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

REVEL

Benign

0.047

Sift

Benign

0.95

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

Sift4G

Benign

1.0

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

Polyphen

0.0

B;B;B;B;B;B;.;.

Vest4

0.037

MutPred

0.51

.;Loss of ubiquitination at K788 (P = 0.0863);Loss of ubiquitination at K788 (P = 0.0863);Loss of ubiquitination at K788 (P = 0.0863);.;Loss of ubiquitination at K788 (P = 0.0863);.;.;

MVP

0.15

MPC

0.068

ClinPred

0.022

GERP RS

3.2

Varity_R

0.030

gMVP

0.20

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