10-30845359-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001143768.2(ZNF438):​c.2089G>A​(p.Ala697Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,614,146 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ZNF438
NM_001143768.2 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.780
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04997188).
BP6
Variant 10-30845359-C-T is Benign according to our data. Variant chr10-30845359-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3820910.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF438NM_001143768.2 linkc.2089G>A p.Ala697Thr missense_variant Exon 7 of 7 ENST00000436087.7 NP_001137240.1 Q7Z4V0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF438ENST00000436087.7 linkc.2089G>A p.Ala697Thr missense_variant Exon 7 of 7 5 NM_001143768.2 ENSP00000406934.2 Q7Z4V0-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152134
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251474
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000272
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1461894
Hom.:
0
Cov.:
32
AF XY:
0.0000165
AC XY:
12
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000126
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000989
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152252
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.0000654
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:
0.0000302
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Feb 15, 2025
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.068
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
0.059
DANN
Benign
0.93
DEOGEN2
Benign
0.016
.;T;T;T;.;T;.;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.54
.;.;.;.;T;T;T;T
M_CAP
Benign
0.0073
T
MetaRNN
Benign
0.050
T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.4
.;L;L;L;.;L;.;.
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-1.1
N;N;N;N;N;N;N;N
REVEL
Benign
0.040
Sift
Benign
0.23
T;T;T;T;T;T;T;T
Sift4G
Benign
0.089
T;T;T;T;T;T;T;T
Polyphen
0.33
B;B;B;B;B;B;.;.
Vest4
0.042
MVP
0.42
MPC
0.068
ClinPred
0.033
T
GERP RS
-4.2
Varity_R
0.019
gMVP
0.23

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.

Other links and lift over

dbSNP: rs374470092; hg19: chr10-31134288; API