19-58455474-A-G

Variant summary

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

The NM_207395.3(ZNF324B):ā€‹c.530A>Gā€‹(p.Lys177Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000053 ( 0 hom., cov: 32)
Exomes š‘“: 0.000040 ( 0 hom. )

Consequence

ZNF324B
NM_207395.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.524
Variant links:
Genes affected
ZNF324B (HGNC:33107): (zinc finger protein 324B) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. 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=0.06041637).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF324BNM_207395.3 linkuse as main transcriptc.530A>G p.Lys177Arg missense_variant 4/4 ENST00000336614.9 NP_997278.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF324BENST00000336614.9 linkuse as main transcriptc.530A>G p.Lys177Arg missense_variant 4/41 NM_207395.3 ENSP00000337473 P1Q6AW86-1
ZNF324BENST00000545523.5 linkuse as main transcriptc.530A>G p.Lys177Arg missense_variant 5/51 ENSP00000438930 P1Q6AW86-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152206
Hom.:
0
Cov.:
32
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:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000598
AC:
15
AN:
250870
Hom.:
0
AF XY:
0.0000811
AC XY:
11
AN XY:
135642
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000124
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000397
AC:
58
AN:
1461758
Hom.:
0
Cov.:
32
AF XY:
0.0000468
AC XY:
34
AN XY:
727172
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000468
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152206
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74368
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:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000113
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.000164
EpiControl
AF:
0.000178

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 submitterclinical testingAmbry GeneticsAug 21, 2023The c.530A>G (p.K177R) alteration is located in exon 4 (coding exon 3) of the ZNF324B gene. This alteration results from a A to G substitution at nucleotide position 530, causing the lysine (K) at amino acid position 177 to be replaced by an arginine (R). 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
0.083
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
3.6
DANN
Uncertain
0.99
DEOGEN2
Benign
0.039
T;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.035
N
LIST_S2
Benign
0.58
.;T
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.060
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.5
L;L
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-1.2
N;N
REVEL
Benign
0.033
Sift
Benign
0.14
T;T
Sift4G
Benign
0.23
T;T
Polyphen
0.060
B;B
Vest4
0.032
MutPred
0.33
Loss of methylation at K177 (P = 0.0034);Loss of methylation at K177 (P = 0.0034);
MVP
0.12
MPC
0.61
ClinPred
0.036
T
GERP RS
-0.80
Varity_R
0.038
gMVP
0.081

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: rs753478474; hg19: chr19-58966841; API