19-11867497-C-T

Variant summary

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

The NM_001348719.2(ZNF439):​c.443C>T​(p.Thr148Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,614,002 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

ZNF439
NM_001348719.2 missense

Scores

2
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.43
Variant links:
Genes affected
ZNF439 (HGNC:20873): (zinc finger protein 439) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [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=0.03920859).
BP6
Variant 19-11867497-C-T is Benign according to our data. Variant chr19-11867497-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3475918.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF439NM_001348719.2 linkc.443C>T p.Thr148Ile missense_variant Exon 4 of 4 ENST00000682736.1 NP_001335648.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF439ENST00000682736.1 linkc.443C>T p.Thr148Ile missense_variant Exon 4 of 4 NM_001348719.2 ENSP00000506930.1 A0A804HI69

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152150
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251380
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135850
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000356
AC:
52
AN:
1461852
Hom.:
0
Cov.:
31
AF XY:
0.0000385
AC XY:
28
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000441
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152150
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.00
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
Nov 22, 2024
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
0.092
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
0.026
DANN
Benign
0.37
DEOGEN2
Benign
0.040
.;T
Eigen
Benign
-1.8
Eigen_PC
Benign
-2.0
FATHMM_MKL
Benign
0.012
N
LIST_S2
Benign
0.15
T;T
M_CAP
Benign
0.00095
T
MetaRNN
Benign
0.039
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.3
.;M
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-3.4
D;D
REVEL
Benign
0.068
Sift
Benign
0.15
T;T
Sift4G
Benign
0.066
T;T
Polyphen
0.013
.;B
Vest4
0.021
MutPred
0.38
.;Loss of phosphorylation at T143 (P = 0.0268);
MVP
0.085
MPC
0.055
ClinPred
0.048
T
GERP RS
-0.91
Varity_R
0.054
gMVP
0.034

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: rs746091527; hg19: chr19-11978312; API