19-58455576-C-T

Variant summary

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

The NM_207395.3(ZNF324B):​c.632C>T​(p.Ser211Leu) 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 1,614,008 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 (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

ZNF324B
NM_207395.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.31
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=0.06320357).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF324BNM_207395.3 linkuse as main transcriptc.632C>T p.Ser211Leu 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.632C>T p.Ser211Leu missense_variant 4/41 NM_207395.3 ENSP00000337473 P1Q6AW86-1
ZNF324BENST00000545523.5 linkuse as main transcriptc.632C>T p.Ser211Leu missense_variant 5/51 ENSP00000438930 P1Q6AW86-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152232
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000319
AC:
8
AN:
251012
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135762
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000705
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000260
AC:
38
AN:
1461776
Hom.:
0
Cov.:
32
AF XY:
0.0000234
AC XY:
17
AN XY:
727194
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000297
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152232
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
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:
0.0000588
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.000109
EpiControl
AF:
0.000237

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 GeneticsApr 22, 2024The c.632C>T (p.S211L) alteration is located in exon 4 (coding exon 3) of the ZNF324B gene. This alteration results from a C to T substitution at nucleotide position 632, causing the serine (S) at amino acid position 211 to be replaced by a leucine (L). 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
0.089
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.86
CADD
Benign
6.0
DANN
Benign
0.79
DEOGEN2
Benign
0.20
T;T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.060
N
LIST_S2
Benign
0.27
.;T
M_CAP
Benign
0.0038
T
MetaRNN
Benign
0.063
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-1.2
N;N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-2.8
D;D
REVEL
Benign
0.016
Sift
Benign
0.11
T;T
Sift4G
Benign
0.17
T;T
Polyphen
0.0
B;B
Vest4
0.078
MutPred
0.30
Loss of phosphorylation at S211 (P = 0.0514);Loss of phosphorylation at S211 (P = 0.0514);
MVP
0.040
MPC
0.66
ClinPred
0.028
T
GERP RS
-0.86
Varity_R
0.049
gMVP
0.068

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: rs752106680; hg19: chr19-58966943; COSMIC: COSV100351694; COSMIC: COSV100351694; API