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GeneBe

19-11948899-C-G

Variant summary

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

The NM_144566.3(ZNF700):c.875C>G(p.Ser292Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,834 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: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZNF700
NM_144566.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.30
Variant links:
Genes affected
ZNF700 (HGNC:25292): (zinc finger protein 700) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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]

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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=0.12536278).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZNF700NM_144566.3 linkuse as main transcriptc.875C>G p.Ser292Cys missense_variant 4/4 ENST00000254321.10
ZNF700NM_001271848.2 linkuse as main transcriptc.884C>G p.Ser295Cys missense_variant 4/4
ZNF69XM_017027231.2 linkuse as main transcriptc.500-31142C>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZNF700ENST00000254321.10 linkuse as main transcriptc.875C>G p.Ser292Cys missense_variant 4/41 NM_144566.3 P2
ENST00000586394.1 linkuse as main transcriptn.69-4083C>G intron_variant, non_coding_transcript_variant 3
ZNF700ENST00000622593.4 linkuse as main transcriptc.884C>G p.Ser295Cys missense_variant 4/44 A2
ZNF700ENST00000482090.1 linkuse as main transcriptc.821C>G p.Ser274Cys missense_variant 3/32 A2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1451834
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
722186
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.01e-7
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000307
Hom.:
0
Bravo
AF:
0.00000378
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 GeneticsDec 26, 2023The c.875C>G (p.S292C) alteration is located in exon 4 (coding exon 4) of the ZNF700 gene. This alteration results from a C to G substitution at nucleotide position 875, causing the serine (S) at amino acid position 292 to be replaced by a cysteine (C). 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
0.17
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.63
Cadd
Benign
1.8
Dann
Benign
0.76
DEOGEN2
Benign
0.066
T;.;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.0
N
LIST_S2
Benign
0.33
T;T;T
M_CAP
Benign
0.0010
T
MetaRNN
Benign
0.13
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-2.3
N;.;.
REVEL
Benign
0.013
Sift
Benign
0.096
T;.;.
Sift4G
Benign
0.062
T;T;T
Polyphen
0.053
B;.;.
Vest4
0.21
MutPred
0.35
Loss of phosphorylation at S292 (P = 0.0256);.;.;
MVP
0.26
MPC
0.0090
ClinPred
0.046
T
GERP RS
-0.94
Varity_R
0.061
gMVP
0.0095

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: rs948011485; hg19: chr19-12059714; COSMIC: COSV54315294; COSMIC: COSV54315294; API