19-58469800-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014347.3(ZNF324):​c.194C>T​(p.Thr65Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000737 in 1,600,864 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000075 ( 1 hom. )

Consequence

ZNF324
NM_014347.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.29
Variant links:
Genes affected
ZNF324 (HGNC:14096): (zinc finger protein 324) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Acts upstream of or within with a positive effect on G1/S transition of mitotic cell cycle and cell population proliferation. Predicted to be active 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 -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.046070755).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF324NM_014347.3 linkc.194C>T p.Thr65Met missense_variant Exon 3 of 4 ENST00000196482.4 NP_055162.1 O75467A0A024R4R8
ZNF324XM_005258713.5 linkc.209C>T p.Thr70Met missense_variant Exon 3 of 4 XP_005258770.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF324ENST00000196482.4 linkc.194C>T p.Thr65Met missense_variant Exon 3 of 4 1 NM_014347.3 ENSP00000196482.3 O75467
ZNF324ENST00000536459.6 linkc.194C>T p.Thr65Met missense_variant Exon 3 of 4 2 ENSP00000444812.1 O75467

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152216
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:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000659
AC:
15
AN:
227498
Hom.:
0
AF XY:
0.0000653
AC XY:
8
AN XY:
122586
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000624
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000365
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000118
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000752
AC:
109
AN:
1448648
Hom.:
1
Cov.:
31
AF XY:
0.0000779
AC XY:
56
AN XY:
719154
show subpopulations
Gnomad4 AFR exome
AF:
0.0000301
Gnomad4 AMR exome
AF:
0.0000468
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000359
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000904
Gnomad4 OTH exome
AF:
0.0000334
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152216
Hom.:
0
Cov.:
33
AF XY:
0.0000403
AC XY:
3
AN XY:
74362
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:
0.0000941
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000450
Hom.:
0
Bravo
AF:
0.0000453
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000124
AC:
15

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 15, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.194C>T (p.T65M) alteration is located in exon 3 (coding exon 2) of the ZNF324 gene. This alteration results from a C to T substitution at nucleotide position 194, causing the threonine (T) at amino acid position 65 to be replaced by a methionine (M). 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
0.11
BayesDel_addAF
Benign
-0.57
T
BayesDel_noAF
Benign
-0.83
CADD
Benign
0.34
DANN
Benign
0.82
DEOGEN2
Benign
0.020
.;T;T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.046
N
LIST_S2
Benign
0.029
T;.;T
M_CAP
Benign
0.0028
T
MetaRNN
Benign
0.046
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.58
.;N;N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.66
.;N;N
REVEL
Benign
0.048
Sift
Benign
0.20
.;T;T
Sift4G
Benign
0.26
T;T;T
Polyphen
0.10
.;B;B
Vest4
0.17
MVP
0.092
MPC
0.71
ClinPred
0.026
T
GERP RS
-7.3
Varity_R
0.018
gMVP
0.074

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: rs149546040; hg19: chr19-58981167; API