4-25314054-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_024936.3(ZCCHC4):c.136C>T(p.Leu46Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,386,422 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
Consequence
NM_024936.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZCCHC4 | ENST00000302874.9 | c.136C>T | p.Leu46Phe | missense_variant | Exon 2 of 13 | 1 | NM_024936.3 | ENSP00000303468.4 | ||
ZCCHC4 | ENST00000505451.5 | n.161C>T | non_coding_transcript_exon_variant | Exon 2 of 9 | 1 | |||||
ZCCHC4 | ENST00000507760.5 | n.136C>T | non_coding_transcript_exon_variant | Exon 2 of 9 | 1 | ENSP00000422115.1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 1AN: 144804Hom.: 0 Cov.: 31 FAILED QC
GnomAD3 exomes AF: 0.00000841 AC: 2AN: 237746Hom.: 0 AF XY: 0.0000155 AC XY: 2AN XY: 129364
GnomAD4 exome AF: 0.0000108 AC: 15AN: 1386422Hom.: 0 Cov.: 29 AF XY: 0.0000130 AC XY: 9AN XY: 692638
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000690 AC: 1AN: 144902Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 69904
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.136C>T (p.L46F) alteration is located in exon 2 (coding exon 2) of the ZCCHC4 gene. This alteration results from a C to T substitution at nucleotide position 136, causing the leucine (L) at amino acid position 46 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at