19-58470812-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014347.3(ZNF324):​c.320C>T​(p.Thr107Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,614,138 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 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

ZNF324
NM_014347.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0420
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 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=0.093352586).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF324NM_014347.3 linkc.320C>T p.Thr107Ile missense_variant Exon 4 of 4 ENST00000196482.4 NP_055162.1 O75467A0A024R4R8
ZNF324XM_005258713.5 linkc.335C>T p.Thr112Ile missense_variant Exon 4 of 4 XP_005258770.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF324ENST00000196482.4 linkc.320C>T p.Thr107Ile missense_variant Exon 4 of 4 1 NM_014347.3 ENSP00000196482.3 O75467
ZNF324ENST00000536459.6 linkc.320C>T p.Thr107Ile missense_variant Exon 4 of 4 2 ENSP00000444812.1 O75467
ZNF324ENST00000593925.1 linkc.-107C>T upstream_gene_variant 2 ENSP00000471778.1 M0R1C8

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152244
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251488
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000267
AC:
39
AN:
1461894
Hom.:
0
Cov.:
30
AF XY:
0.0000193
AC XY:
14
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000315
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152244
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74374
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000189
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 21, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.320C>T (p.T107I) alteration is located in exon 4 (coding exon 3) of the ZNF324 gene. This alteration results from a C to T substitution at nucleotide position 320, causing the threonine (T) at amino acid position 107 to be replaced by an isoleucine (I). 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
0.16
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
4.3
DANN
Benign
0.83
DEOGEN2
Benign
0.047
.;T;T
Eigen
Benign
-0.79
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.30
N
LIST_S2
Benign
0.73
T;.;T
M_CAP
Benign
0.0057
T
MetaRNN
Benign
0.093
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.2
.;L;L
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-1.6
.;N;N
REVEL
Benign
0.038
Sift
Benign
0.48
.;T;T
Sift4G
Uncertain
0.043
D;T;T
Polyphen
0.44
.;B;B
Vest4
0.14
MutPred
0.30
Loss of disorder (P = 0.0324);Loss of disorder (P = 0.0324);Loss of disorder (P = 0.0324);
MVP
0.32
MPC
0.83
ClinPred
0.099
T
GERP RS
2.1
Varity_R
0.063
gMVP
0.21

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: rs1483914968; hg19: chr19-58982179; API