chr18-74631683-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_017757.3(ZNF407):c.664C>T(p.His222Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
Consequence
ZNF407
NM_017757.3 missense
NM_017757.3 missense
Scores
2
12
Clinical Significance
Conservation
PhyloP100: 3.23
Genes affected
ZNF407 (HGNC:19904): (zinc finger protein 407) This gene encodes a zinc finger protein whose exact function is not known. It may be involved in transcriptional regulation. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]
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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=0.16308281).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF407 | NM_017757.3 | c.664C>T | p.His222Tyr | missense_variant | 2/9 | ENST00000299687.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF407 | ENST00000299687.10 | c.664C>T | p.His222Tyr | missense_variant | 2/9 | 1 | NM_017757.3 | P2 | |
ZNF407 | ENST00000577538.5 | c.664C>T | p.His222Tyr | missense_variant | 1/7 | 2 | A2 | ||
ZNF407 | ENST00000309902.10 | c.664C>T | p.His222Tyr | missense_variant | 1/4 | 2 | |||
ZNF407 | ENST00000582337.5 | c.664C>T | p.His222Tyr | missense_variant | 2/5 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 60
GnomAD4 exome
Cov.:
60
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 16, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
Sift4G
Benign
T;T;T;T
Polyphen
D;D;D;D
Vest4
MutPred
Loss of methylation at K223 (P = 0.0585);Loss of methylation at K223 (P = 0.0585);Loss of methylation at K223 (P = 0.0585);Loss of methylation at K223 (P = 0.0585);
MVP
MPC
0.12
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at