4-25361919-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_024936.3(ZCCHC4):c.1072G>A(p.Val358Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,786 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 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
ZCCHC4
NM_024936.3 missense
NM_024936.3 missense
Scores
8
7
4
Clinical Significance
Conservation
PhyloP100: 8.68
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 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.849
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ZCCHC4 | NM_024936.3 | c.1072G>A | p.Val358Met | missense_variant | 9/13 | ENST00000302874.9 | NP_079212.2 | |
ZCCHC4 | XM_011513835.3 | c.1117G>A | p.Val373Met | missense_variant | 10/14 | XP_011512137.1 | ||
ZCCHC4 | XM_017008129.3 | c.820G>A | p.Val274Met | missense_variant | 7/11 | XP_016863618.1 | ||
ZCCHC4 | XR_925324.4 | n.1153G>A | non_coding_transcript_exon_variant | 10/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZCCHC4 | ENST00000302874.9 | c.1072G>A | p.Val358Met | missense_variant | 9/13 | 1 | NM_024936.3 | ENSP00000303468 | P1 | |
ZCCHC4 | ENST00000507760.5 | c.*57G>A | 3_prime_UTR_variant, NMD_transcript_variant | 6/9 | 1 | ENSP00000422115 | ||||
ZCCHC4 | ENST00000505412.1 | c.667G>A | p.Val223Met | missense_variant | 6/10 | 3 | ENSP00000422269 | |||
ZCCHC4 | ENST00000508058.1 | n.211G>A | non_coding_transcript_exon_variant | 1/4 | 4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249074Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135128
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461682Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727138
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74300
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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 | Sep 01, 2021 | The c.1072G>A (p.V358M) alteration is located in exon 9 (coding exon 9) of the ZCCHC4 gene. This alteration results from a G to A substitution at nucleotide position 1072, causing the valine (V) at amino acid position 358 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
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