chr4-25362245-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_024936.3(ZCCHC4):c.1153C>T(p.Arg385Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,610,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
ZCCHC4
NM_024936.3 missense
NM_024936.3 missense
Scores
3
12
4
Clinical Significance
Conservation
PhyloP100: 2.51
Genes affected
ZCCHC4 (HGNC:22917): (zinc finger CCHC-type containing 4) Enables S-adenosyl-L-methionine binding activity; rRNA (adenine-N6-)-methyltransferase activity; and zinc ion binding activity. Involved in positive regulation of translation and rRNA methylation. Located in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.815
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZCCHC4 | NM_024936.3 | c.1153C>T | p.Arg385Trp | missense_variant | 10/13 | ENST00000302874.9 | |
ZCCHC4 | XM_011513835.3 | c.1198C>T | p.Arg400Trp | missense_variant | 11/14 | ||
ZCCHC4 | XM_017008129.3 | c.901C>T | p.Arg301Trp | missense_variant | 8/11 | ||
ZCCHC4 | XR_925324.4 | n.1234C>T | non_coding_transcript_exon_variant | 11/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZCCHC4 | ENST00000302874.9 | c.1153C>T | p.Arg385Trp | missense_variant | 10/13 | 1 | NM_024936.3 | P1 | |
ZCCHC4 | ENST00000507760.5 | c.*138C>T | 3_prime_UTR_variant, NMD_transcript_variant | 7/9 | 1 | ||||
ZCCHC4 | ENST00000505412.1 | c.748C>T | p.Arg250Trp | missense_variant | 7/10 | 3 | |||
ZCCHC4 | ENST00000508058.1 | n.292C>T | non_coding_transcript_exon_variant | 2/4 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152172Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000603 AC: 15AN: 248690Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 134974
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GnomAD4 exome AF: 0.0000233 AC: 34AN: 1458812Hom.: 0 Cov.: 29 AF XY: 0.0000234 AC XY: 17AN XY: 725750
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152172Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74338
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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 submitter | clinical testing | Ambry Genetics | Mar 07, 2023 | The c.1153C>T (p.R385W) alteration is located in exon 10 (coding exon 10) of the ZCCHC4 gene. This alteration results from a C to T substitution at nucleotide position 1153, causing the arginine (R) at amino acid position 385 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at