19-47066522-T-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_015168.2(ZC3H4):c.3746A>G(p.Asn1249Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,571,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_015168.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZC3H4 | NM_015168.2 | c.3746A>G | p.Asn1249Ser | missense_variant | 15/15 | ENST00000253048.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZC3H4 | ENST00000253048.10 | c.3746A>G | p.Asn1249Ser | missense_variant | 15/15 | 1 | NM_015168.2 | P1 | |
ZC3H4 | ENST00000601973.1 | c.2567A>G | p.Asn856Ser | missense_variant | 8/8 | 5 | |||
ZC3H4 | ENST00000594019.5 | n.1596A>G | non_coding_transcript_exon_variant | 7/7 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152042Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000600 AC: 12AN: 199856Hom.: 0 AF XY: 0.0000464 AC XY: 5AN XY: 107652
GnomAD4 exome AF: 0.0000493 AC: 70AN: 1419794Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 27AN XY: 700938
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152042Hom.: 0 Cov.: 33 AF XY: 0.0000539 AC XY: 4AN XY: 74268
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2022 | The c.3746A>G (p.N1249S) alteration is located in exon 15 (coding exon 14) of the ZC3H4 gene. This alteration results from a A to G substitution at nucleotide position 3746, causing the asparagine (N) at amino acid position 1249 to be replaced by a serine (S). 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