19-58455249-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_207395.3(ZNF324B):​c.305C>T​(p.Pro102Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,614,066 control chromosomes in the GnomAD database, including 2 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 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 2 hom. )

Consequence

ZNF324B
NM_207395.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0550
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.028111875).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF324BNM_207395.3 linkuse as main transcriptc.305C>T p.Pro102Leu 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.305C>T p.Pro102Leu missense_variant 4/41 NM_207395.3 ENSP00000337473 P1Q6AW86-1
ZNF324BENST00000545523.5 linkuse as main transcriptc.305C>T p.Pro102Leu missense_variant 5/51 ENSP00000438930 P1Q6AW86-1
ZNF324BENST00000599193.5 linkuse as main transcriptc.305C>T p.Pro102Leu missense_variant 4/43 ENSP00000473115
ZNF324BENST00000599194.5 linkuse as main transcriptc.305C>T p.Pro102Leu missense_variant 4/44 ENSP00000472178

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152180
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:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000127
AC:
32
AN:
251466
Hom.:
2
AF XY:
0.000169
AC XY:
23
AN XY:
135916
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:
0.00101
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000342
AC:
50
AN:
1461886
Hom.:
2
Cov.:
31
AF XY:
0.0000536
AC XY:
39
AN XY:
727244
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:
0.000499
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152180
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74330
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:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.000107
AC:
13

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 12, 2021The c.305C>T (p.P102L) 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 305, causing the proline (P) at amino acid position 102 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
0.068
BayesDel_addAF
Benign
-0.58
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
1.2
DANN
Benign
0.25
DEOGEN2
Benign
0.023
T;T;.;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.033
N
LIST_S2
Benign
0.64
.;T;T;T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.028
T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.76
N;N;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.26
N;N;.;.
REVEL
Benign
0.029
Sift
Benign
0.46
T;T;.;.
Sift4G
Benign
0.29
T;T;T;T
Polyphen
0.0020
B;B;.;.
Vest4
0.070
MutPred
0.30
Loss of disorder (P = 0.0182);Loss of disorder (P = 0.0182);Loss of disorder (P = 0.0182);Loss of disorder (P = 0.0182);
MVP
0.26
MPC
0.77
ClinPred
0.014
T
GERP RS
1.4
Varity_R
0.048
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs745545576; hg19: chr19-58966616; API