16-4752851-T-A

Variant summary

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

The NM_021646.4(ZNF500):​c.968A>T​(p.Lys323Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ZNF500
NM_021646.4 missense

Scores

3
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.128
Variant links:
Genes affected
ZNF500 (HGNC:23716): (zinc finger protein 500) 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. Located in cytosol and nucleoplasm. [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=0.15906069).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF500NM_021646.4 linkc.968A>T p.Lys323Met missense_variant 6/6 ENST00000219478.11 NP_067678.1 O60304-1
ZNF500NM_001303450.2 linkc.968A>T p.Lys323Met missense_variant 6/7 NP_001290379.1 O60304-2
ZNF500XM_011522453.3 linkc.968A>T p.Lys323Met missense_variant 6/7 XP_011520755.1
ZNF500XM_005255243.5 linkc.617A>T p.Lys206Met missense_variant 5/5 XP_005255300.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF500ENST00000219478.11 linkc.968A>T p.Lys323Met missense_variant 6/62 NM_021646.4 ENSP00000219478.5 O60304-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152224
Hom.:
0
Cov.:
34
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:
0.000827
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251140
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135836
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:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000185
AC:
27
AN:
1461838
Hom.:
0
Cov.:
33
AF XY:
0.0000234
AC XY:
17
AN XY:
727214
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:
0.000267
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152224
Hom.:
0
Cov.:
34
AF XY:
0.0000538
AC XY:
4
AN XY:
74378
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:
0.000827
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000247
AC:
3

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 GeneticsOct 13, 2023The c.968A>T (p.K323M) alteration is located in exon 6 (coding exon 5) of the ZNF500 gene. This alteration results from a A to T substitution at nucleotide position 968, causing the lysine (K) at amino acid position 323 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
Pathogenic
0.91
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Benign
0.31
T;.;T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.56
FATHMM_MKL
Benign
0.45
N
LIST_S2
Uncertain
0.86
D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.16
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Pathogenic
3.7
H;H;.
PrimateAI
Uncertain
0.66
T
PROVEAN
Pathogenic
-4.7
D;D;.
REVEL
Benign
0.099
Sift
Uncertain
0.0010
D;D;.
Sift4G
Uncertain
0.0070
D;D;D
Polyphen
0.98
D;.;.
Vest4
0.29
MutPred
0.35
Loss of methylation at K323 (P = 0.0012);Loss of methylation at K323 (P = 0.0012);.;
MVP
0.35
MPC
0.29
ClinPred
0.81
D
GERP RS
2.8
Varity_R
0.20
gMVP
0.18

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: rs757621153; hg19: chr16-4802852; API